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Sample records for mouse strain ntl

  1. A Rebuttal of NTL Institute's Learning Pyramid

    ERIC Educational Resources Information Center

    Letrud, Kare

    2012-01-01

    This article discusses the learning pyramid corroborated by National Training Laboratories Institute. It present and compliment historical and methodological critique against the learning pyramid, and call upon NTL Institute ought to retract their model.

  2. Subcellular Distribution of NTL Transcription Factors in Arabidopsis thaliana.

    PubMed

    Liang, Mingwei; Li, Hongjuan; Zhou, Fang; Li, Huiyong; Liu, Jin; Hao, Yi; Wang, Yingdian; Zhao, Heping; Han, Shengcheng

    2015-10-01

    NAC with a transmembrane (TM) motif1-like (NTL) transcription factors, containing three regions: the N-terminal NAC domain (ND), the middle regulation region (RR), and the C-terminal TM domain, belong to the tail-anchored proteins. Although these NTLs play numerous essential roles in plants, their subcellular distribution and the mechanism of translocation into the nucleus (NU) remain unclear. In this study, we found that most of the full-length NTLs were localized in the endoplasmic reticulum (ER), with the exception of NTL11 and NTL5, which were restricted to the NU. Furthermore, we found that NTL11 contains a TM domain, whereas NTL5 does not. The ND of all of the NTLs was responsible for nuclear localization in plants. After truncation of the TM domain, NTL8_NR, NTL10_NR and NTL13_NR localized in the cytoplasm (CT) and NU, and other NTL_NRs were only localized in the NU, suggesting that the RR of NTL8, NTL10 and NTL13 contains some inhibitory region to mask the nuclear localization signal sequence in the ND domain and permit their diffusion between CT and NU. Furthermore, the N-terminus of NTL11 was translocated to the NU, but the C-terminus was degraded in Arabidopsis mesophyll protoplasts. The chimeric construct of NTL11_ND with NTL10_RR and TM domain (11ND-10RT) was localized exclusively in the ER, and not in the NU. However, 10ND-11RT was found mainly in the NU. Our results indicated that the TM domain is essential for NTL targeting the ER and the N-terminal fragment, including ND and RR, is translocated into the NU after activation through proteolytic cleavage events upon stimulation by internal and external environmental signals. PMID:26201836

  3. Genealogies of mouse inbred strains.

    PubMed

    Beck, J A; Lloyd, S; Hafezparast, M; Lennon-Pierce, M; Eppig, J T; Festing, M F; Fisher, E M

    2000-01-01

    The mouse is a prime organism of choice for modelling human disease. Over 450 inbred strains of mice have been described, providing a wealth of different genotypes and phenotypes for genetic and other studies. As new strains are generated and others become extinct, it is useful to review periodically what strains are available and how they are related to each other, particularly in the light of available DNA polymorphism data from microsatellite and other markers. We describe the origins and relationships of inbred mouse strains, 90 years after the generation of the first inbred strain. Given the large collection of inbred strains available, and that published information on these strains is incomplete, we propose that all genealogical and genetic data on inbred strains be submitted to a common electronic database to ensure this valuable information resource is preserved and used efficiently. PMID:10615122

  4. Fancy Ideas on Neganov-Trofimov Luke Effect (NTL) or: Is There a Limit to the NTL Amplification?

    NASA Astrophysics Data System (ADS)

    Chapellier, M. P.

    2015-02-01

    The limits on the NTL effect are due to parasitic currents from the electrodes entering the semiconductor. An implanted diode is known to have a better surface behaviour and a very high amplification. One can imagine also to separate the electrodes from the semiconductor. An avalanche structure could also be fabricated to multiply the number of electrons produced before using them. Some applications are suggested.

  5. Biological Basis of Differential Susceptibility to Hepatocarcinogenesis among Mouse Strains*

    PubMed Central

    Maronpot, Robert R.

    2009-01-01

    There is a vast amount of literature related to mouse liver tumorigenesis generated over the past 60 years, not all of which has been captured here. The studies reported in this literature have generally been state of the art at the time they were carried out. A PubMed search on the topic “mouse liver tumors” covering the past 10 years yields over 7000 scientific papers. This review address several important topics related to the unresolved controversy regarding the relevance of mouse liver tumor responses observed in cancer bioassays. The inherent mouse strain differential sensitivities to hepatocarcinogenesis largely parallel the strain susceptibility to chemically induced liver neoplasia. The effects of phenobarbital and halogenated hydrocarbons in mouse hepatocarcinogenesis have been summarized because of recurring interest and numerous publications on these topics. No single simple paradigm fully explains differential mouse strain responses, which can vary more than 50-fold among inbred strains. In addition to inherent genetics, modifying factors including cell cycle balance, enzyme induction, DNA methylation, oncogenes and suppressor genes, diet, and intercellular communication influence susceptibility to spontaneous and induced mouse hepatocarcinogenesis. Comments are offered on the evaluation, interpretation, and relevance of mouse liver tumor responses in the context of cancer bioassays. PMID:22271974

  6. The International Mouse Strain Resource (IMSR): cataloging worldwide mouse and ES cell line resources.

    PubMed

    Eppig, Janan T; Motenko, Howie; Richardson, Joel E; Richards-Smith, Beverly; Smith, Cynthia L

    2015-10-01

    The availability of and access to quality genetically defined, health-status known mouse resources is critical for biomedical research. By ensuring that mice used in research experiments are biologically, genetically, and health-status equivalent, we enable knowledge transfer, hypothesis building based on multiple data streams, and experimental reproducibility based on common mouse resources (reagents). Major repositories for mouse resources have developed over time and each has significant unique resources to offer. Here we (a) describe The International Mouse Strain Resource that offers users a combined catalog of worldwide mouse resources (live, cryopreserved, embryonic stem cells), with direct access to repository sites holding resources of interest and (b) discuss the commitment to nomenclature standards among resources that remain a challenge in unifying mouse resource catalogs. PMID:26373861

  7. Differences in oocyte development and estradiol sensitivity among mouse strains.

    PubMed

    Pepling, Melissa E; Sundman, Emily A; Patterson, Nicole L; Gephardt, Grant W; Medico, Leonard; Wilson, Krystal I

    2010-02-01

    Mouse oocytes develop in clusters of interconnected cells called germline cysts. Shortly after birth, the majority of cysts break apart and primordial follicles form, consisting of one oocyte surrounded by granulosa cells. Concurrently, oocyte number is reduced by two-thirds. Exposure of neonatal females to estrogenic compounds causes multiple oocyte follicles that are likely germline cysts that did not break down. Supporting this idea, estrogen disrupts cyst breakdown and may regulate normal oocyte development. Previously, the CD-1 strain was used to study cyst breakdown and oocyte survival, but it is unknown if there are differences in these processes in other mouse strains. It is also unknown if there are variations in estrogen sensitivity during oocyte development. Here, we examined neonatal oocyte development in FVB, C57BL/6, and F2 hybrid (Oct4-GFP) strains, and compared them with the CD-1 strain. We found variability in oocyte development among the four strains. We also investigated estrogen sensitivity differences, and found that C57BL/6 ovaries are more sensitive to estradiol than CD-1, FVB, or Oct4-GFP ovaries. Insight into differences in oocyte development will facilitate comparison of mice generated on different genetic backgrounds. Understanding variations in estrogen sensitivity will lead to better understanding of the risks of environmental estrogen exposure in humans. PMID:19846484

  8. Disparate metabolic response to fructose feeding between different mouse strains

    PubMed Central

    Montgomery, M. K.; Fiveash, C. E.; Braude, J. P.; Osborne, B.; Brown, S. H. J.; Mitchell, T. W.; Turner, N.

    2015-01-01

    Diets enriched in fructose (FR) increase lipogenesis in the liver, leading to hepatic lipid accumulation and the development of insulin resistance. Previously, we have shown that in contrast to other mouse strains, BALB/c mice are resistant to high fat diet-induced metabolic deterioration, potentially due to a lack of ectopic lipid accumulation in the liver. In this study we have compared the metabolic response of BALB/c and C57BL/6 (BL6) mice to a fructose-enriched diet. Both strains of mice increased adiposity in response to FR-feeding, while only BL6 mice displayed elevated hepatic triglyceride (TAG) accumulation and glucose intolerance. The lack of hepatic TAG accumulation in BALB/c mice appeared to be linked to an altered balance between lipogenic and lipolytic pathways, while the protection from fructose-induced glucose intolerance in this strain was likely related to low levels of ER stress, a slight elevation in insulin levels and an altered profile of diacylglycerol species in the liver. Collectively these findings highlight the multifactorial nature of metabolic defects that develop in response to changes in the intake of specific nutrients and the divergent response of different mouse strains to dietary challenges. PMID:26690387

  9. Characterization of a mouse-adapted Staphylococcus aureus strain.

    PubMed

    Holtfreter, Silva; Radcliff, Fiona J; Grumann, Dorothee; Read, Hannah; Johnson, Sarah; Monecke, Stefan; Ritchie, Stephen; Clow, Fiona; Goerke, Christiane; Bröker, Barbara M; Fraser, John D; Wiles, Siouxsie

    2013-01-01

    More effective antibiotics and a protective vaccine are desperately needed to combat the 'superbug' Staphylococcus aureus. While in vivo pathogenicity studies routinely involve infection of mice with human S. aureus isolates, recent genetic studies have demonstrated that S. aureus lineages are largely host-specific. The use of such animal-adapted S. aureus strains may therefore be a promising approach for developing more clinically relevant animal infection models. We have isolated a mouse-adapted S. aureus strain (JSNZ) which caused a severe outbreak of preputial gland abscesses among male C57BL/6J mice. We aimed to extensively characterize this strain on a genomic level and determine its virulence potential in murine colonization and infection models. JSNZ belongs to the MLST type ST88, rare among human isolates, and lacks an hlb-converting phage encoding human-specific immune evasion factors. Naive mice were found to be more susceptible to nasal and gastrointestinal colonization with JSNZ than with the human-derived Newman strain. Furthermore, naïve mice required antibiotic pre-treatment to become colonized with Newman. In contrast, JSNZ was able to colonize mice in the absence of antibiotic treatment suggesting that this strain can compete with the natural flora for space and nutrients. In a renal abscess model, JSNZ caused more severe disease than Newman with greater weight loss and bacterial burden. In contrast to most other clinical isolates, JSNZ can also be readily genetically modified by phage transduction and electroporation. In conclusion, the mouse-adapted strain JSNZ may represent a valuable tool for studying aspects of mucosal colonization and for screening novel vaccines and therapies directed at preventing colonization. PMID:24023720

  10. The super super-healing MRL mouse strain

    PubMed Central

    HEYDEMANN, Ahlke

    2013-01-01

    The Murphy Roths Large (MRL/MpJ) mice provide unique insights into wound repair and regeneration. These mice and the closely related MRL/MpJ-Faslpr/J and Large strains heal wounds made in multiple tissues without production of a fibrotic scar. The precise mechanism of this remarkable ability still eludes researchers, but some data has been generated and insights are being revealed. For example, MRL cells reepithelialize over dermal wound sites faster than cells of other mouse strains. This allows a blastema to develop beneath the protective layer. The MRL mice also have an altered basal immune system and an altered immune response to injury. In addition, MRL mice have differences in their tissue resident progenitor cells and certain cell cycle regulatory proteins. The difficulty often lies in separating the causative differences from the corollary differences. Remarkably, not every tissue in these mice heals scarlessly, and the specific type of wound and priming affect regeneration ability as well. The MRL/MpJ, MRL/MpJ-Faslpr/J, and Large mouse strains are also being investigated for their autoimmune characteristic. Whether the two phenotypes of regeneration and autoimmunity are related remains an enigma. PMID:24163690

  11. Mouse Genetic Nomenclature: Standardization of Strain, Gene, and Protein Symbols

    PubMed Central

    Sundberg, John P.; Schofield, Paul N

    2011-01-01

    The use of standard nomenclatures for describing the strains, genes, and proteins of species is vital for the interpretation, archiving, analysis, and recovery of experimental data on the laboratory mouse. At a time when sharing of data and meta- analysis of experimental results is becoming a dominant mode of scientific investigation, failure to respect formal nomenclatures can cause confusion, errors, and in some cases contribute to poor science. Here we present the basic nomenclature rules for laboratory mice and explain how these rules should be applied to complex genetic manipulations and crosses. PMID:20685919

  12. Withdrawal severity after chronic intermittent ethanol in inbred mouse strains

    PubMed Central

    Metten, Pamela; Sorensen, Michelle L.; Cameron, Andy Jade; Yu, Chia-Hua; Crabbe, John C.

    2010-01-01

    Background To study withdrawal, ethanol is usually administered chronically without interruption. However, interest has recurred in models of episodic exposure. Increasing evidence suggests that chronic intermittent exposure to ethanol leads to a sensitization effect in both withdrawal severity and in ethanol consumption. The goal of the present study was to examine mouse inbred strain differences in withdrawal severity following chronic intermittent exposure using the handling induced convulsion as the behavioral endpoint. We also sought to compare the withdrawal responses of inbred strains across acute, chronic continuous, and chronic intermittent exposure regimens. Methods Male mice from 15 standard inbred strains were exposed to ethanol vapor for 16 hours each day for 3 days and removed to an air chamber during the intervening 8 hours. Mice in the control groups were handled the same, except that they were exposed only to air. Daily blood ethanol concentrations were averaged for each mouse to estimate total dose of ethanol experienced. Results Across strains, mice had an average daily blood ethanol concentration (BEC) of 1.45 ± 0.02 mg/ml and we restricted the range of this value to 1.00 to 2.00 mg/ml. To evaluate strain differences, we divided data into two dose groups based on BEC, Low Dose (1.29 ± 0.1 mg/ml) and High Dose (1.71 ± 0.02 mg/ml). After the third inhalation exposure, ethanol- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at hr 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of air control values) in both dose groups. Conclusion The chronic intermittent exposure paradigm is sufficient to elicit differential withdrawal responses across nearly all strains. Data from the High Dose groups correlated well with withdrawal data derived from prior acute (single high dose) and chronic continuous (for 72 hrs) ethanol withdrawal studies, supporting the influence of common

  13. Genome analysis of enterovirus 71 strains differing in mouse pathogenicity.

    PubMed

    Li, Peng; Yue, Yingying; Song, Nannan; Li, Bingqing; Meng, Hong; Yang, Guiwen; Li, Zhihui; An, Liguo; Qin, Lizeng

    2016-04-01

    Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) and is occasionally associated with severe neurological diseases. The investigation of virulence determinants of EV71 is rudimentary. Therefore, it is important to understand the relationship between EV71 virulence and genomic information. In this study, a series of analyses about full-length genomic sequence were performed on six EV71 strains isolated from HFMD patients with either severe or mild clinical symptoms. A one-day-old BALB/c mouse model was used to study the infection characteristics. Results showed all six strains were of the subgenogroup C4a. Viral full-length genomic sequence analysis showed that a total of 40 nucleotide differences between strains of highly and low virulence were revealed. Among all mutations, three nucleotide mutations were found in the untranslated region. A mutation, nt115, at internal ribozyme entry site (IRES) caused RNA secondary structural change. The other 37 mutations were all located in the open reading frame resulting in 8 amino acid mutations. Importantly, we discovered that a mutation of amino acid (Asn1617 → Asp1617) in the 3C proteinase (3C(pro)) of highly and low pathogenic strains could lead to conformational change at the active center, suggesting that this site may be a virulence determinant of EV71. PMID:26781949

  14. Strain differences in the response of the mouse to diethylstilbestrol.

    PubMed

    Greenman, D L; Dooley, K; Breeden, C R

    1977-10-01

    BALB/c StCrlfC3Hf/Nctr, C57BL/6/, C57BL/6 X BALB/c F1 hybrid (B6CF1), and monohybrid-cross offspring from the breeding of B6CF1 mice were examined with respect to uterine, vaginal, and thymus responses to diethylstilbestrol (DES). About 400 mice of each genetic population were used. Weanling mice were fed DES at dietary concentrations of 2.5 to 1,000 ppb (microgram/kg feed) for 6 days and were killed by cervical dislocation about 20 hr after removal of the feed. C57BL/6, B6CF1, and the monohybrid-cross offspring did not differ in the uterine-weight response to DES, but the slope of the dose-response line was shallower for the BALB/c than for the other strains. Dietary DES concentrations of 250 ppb or more inhibited the uterotrophic response in all populations. Vaginal cornification occurred at lower concentrations of DES in the C57BL/6 strain than in the B6CF1 animals. BALB/c and monohybrid-cross offspring were indistinguishable from each other in their vaginal response to Des and were less sensitive to DES than the other mouse populations. The use of ethanol or corn oil as the solvent for mixing DES into the diet had no apparent effect on the uterine weight or vaginal response in any of the mice. DES depressed thymus weight in a dose-related fashion at dietary concentrations of 100 ppb and above in all genetic populations. PMID:926210

  15. The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains.

    PubMed

    Collins, Andrew M; Wang, Yan; Roskin, Krishna M; Marquis, Christopher P; Jackson, Katherine J L

    2015-09-01

    The human and mouse antibody repertoires are formed by identical processes, but like all small animals, mice only have sufficient lymphocytes to express a small part of the potential antibody repertoire. In this study, we determined how the heavy chain repertoires of two mouse strains are generated. Analysis of IgM- and IgG-associated VDJ rearrangements generated by high-throughput sequencing confirmed the presence of 99 functional immunoglobulin heavy chain variable (IGHV) genes in the C57BL/6 genome, and inferred the presence of 164 IGHV genes in the BALB/c genome. Remarkably, only five IGHV sequences were common to both strains. Compared with humans, little N nucleotide addition was seen in the junctions of mouse VDJ genes. Germline human IgG-associated IGHV genes are rare, but many murine IgG-associated IGHV genes were unmutated. Together these results suggest that the expressed mouse repertoire is more germline-focused than the human repertoire. The apparently divergent germline repertoires of the mouse strains are discussed with reference to reports that inbred mouse strains carry blocks of genes derived from each of the three subspecies of the house mouse. We hypothesize that the germline genes of BALB/c and C57BL/6 mice may originally have evolved to generate distinct germline-focused antibody repertoires in the different mouse subspecies. PMID:26194750

  16. Comparison of three methods of calculating strain in the mouse ulna in exogenous loading studies.

    PubMed

    Norman, Stephanie C; Wagner, David W; Beaupre, Gary S; Castillo, Alesha B

    2015-01-01

    Axial compression of mouse limbs is commonly used to induce bone formation in a controlled, non-invasive manner. Determination of peak strains caused by loading is central to interpreting results. Load-strain calibration is typically performed using uniaxial strain gauges attached to the diaphyseal, periosteal surface of a small number of sacrificed animals. Strain is measured as the limb is loaded to a range of physiological loads known to be anabolic to bone. The load-strain relationship determined by this subgroup is then extrapolated to a larger group of experimental mice. This method of strain calculation requires the challenging process of strain gauging very small bones which is subject to variability in placement of the strain gauge. We previously developed a method to estimate animal-specific periosteal strain during axial ulnar loading using an image-based computational approach that does not require strain gauges. The purpose of this study was to compare the relationship between load-induced bone formation rates and periosteal strain at ulnar midshaft using three different methods to estimate strain: (A) Nominal strain values based solely on load-strain calibration; (B) Strains calculated from load-strain calibration, but scaled for differences in mid-shaft cross-sectional geometry among animals; and (C) An alternative image-based computational method for calculating strains based on beam theory and animal-specific bone geometry. Our results show that the alternative method (C) provides comparable correlation between strain and bone formation rates in the mouse ulna relative to the strain gauge-dependent methods (A and B), while avoiding the need to use strain gauges. PMID:25443882

  17. Forty mouse strain survey of water and sodium intake

    PubMed Central

    Tordoff, Michael G.; Bachmanov, Alexander A.; Reed, Danielle R.

    2007-01-01

    We measured voluntary water and sodium intakes of 40 inbred strains of mice. Groups of ~10 males and ~10 females from each strain received a series of 48-h tests with a choice between a bottle of water and a bottle of one of the following: water, 25, 75, and 225 mM NaCl, 25, 75, and 225 sodium lactate. Sodium solution intakes were influenced by strain, sex, anion and concentration: Nine strains drank significantly more chloride than lactate, and only one strain (I/LnJ) drank significantly more lactate than chloride. The other 30 strains drank similar volumes of chloride and lactate. Sodium intakes were higher in females than males of 8 strains and did not differ by sex in the other 32 strains. Some strains had consistently high sodium intakes and preferred all sodium solutions to water (129S1/SvImJ, MA/MyJ, NZW/LacJ and SWR/J), some showed indifference (i.e. preferences not significantly different from 50%) to all concentrations tested (A/J, C57BL/6J, FVB/NJ and SEA/GnJ), and some had consistently low sodium intakes (AKR/J, C3H/HeJ, C57BL/10J, CBA/J, DBA/2J, I/LnJ, JF1/Ms, LP/J, NON/LtJ, PERA/EiJ, PL/J, and RIIIS/J). The results illustrate the diversity of voluntary sodium intake in mice and will assist in the selection of appropriate strains for focused genetic and physiological analyses. PMID:17490693

  18. Genetic typing of the senescence-accelerated mouse (SAM) strains with microsatellite markers.

    PubMed

    Xia, C; Higuchi, K; Shimizu, M; Matsushita, T; Kogishi, K; Wang, J; Chiba, T; Festing, M F; Hosokawa, M

    1999-03-01

    The Senescence-Accelerated Mouse (SAM) strains constitute a murine model of accelerated senescence originating from the ancestral AKR/J strains and consist of nine senescence-prone (SAMP) strains and four senescence-resistant (SAMR) strains. The chromosomes (Chrs) of the SAM strains were typed with 581 microsatellite markers amplified by PCR, and the fundamental genetic information of the SAM strains was obtained. One-third of the examined markers displayed polymorphism among the strains, and only two alleles were detected in almost all loci among the SAM and AKR/J strains. However, in 12 loci (5.6% of total 215 polymorphic markers), the third allele was detected among the SAM strains. The genetic typing and developmental history suggested that the SAM strains were related inbred strains developed by the accidental crossing between the AKR/J strain and other unknown strain(s). Comparison of the distribution of the loci in the SAMP and the SAMR series revealed notable differences in the four regions on Chrs 4, 14, 16, and 17. This indicated that some of these chromosomal sites might contain the genes responsible for accelerated senescence in the SAMP series. PMID:10051317

  19. Non-contact strain measurement in the mouse forearm loading model using digital image correlation (DIC).

    PubMed

    Begonia, Mark T; Dallas, Mark; Vizcarra, Bruno; Liu, Ying; Johnson, Mark L; Thiagarajan, Ganesh

    2015-12-01

    This study investigates the use of a non-contact method known as digital image correlation (DIC) to measure strains in the mouse forearm during axial compressive loading. A two camera system was adapted to analyze the medial and lateral forearm displacements simultaneously, and the derived DIC strain measurements were compared to strain gage readings from both the ulna and radius. Factors such as region-of-interest (ROI) location, lens magnification, noise, and out-of-plane motion were examined to determine their influence on the DIC strain measurements. We confirmed that our DIC system can differentiate ROI locations since it detected higher average strains in the ulna compared to the radius and detected compressive strains on medial bone surfaces vs. tensile strains on lateral bone surfaces. Interestingly, the DIC method also captured heterogeneity in surface strain fields which are not detectable by strain gage based methods. A separate analysis of the noise intrinsic to the DIC system also revealed that the noise constituted less than 4.5% of all DIC strain measurements. Furthermore, finite element (FE) simulations of the forearm showed that out-of-plane motion was not a significant factor that influenced DIC measurements. Finally, we observed that average DIC strain measurements can be up to 1.5-2 times greater than average strain gage readings on the medial bone surfaces. These findings suggest that strain experienced in the mouse forearm model by loading is better captured through DIC as opposed to strain gages, which as a result of being glued to the bone surface artificially stiffen the bone and lead to an underestimation of the strain response. PMID:26388521

  20. Mouse strain specific gene expression differences for illumina microarray expression profiling in embryos

    PubMed Central

    2012-01-01

    Background In the field of mouse genetics the advent of technologies like microarray based expression profiling dramatically increased data availability and sensitivity, yet these advanced methods are often vulnerable to the unavoidable heterogeneity of in vivo material and might therefore reflect differentially expressed genes between mouse strains of no relevance to a targeted experiment. The aim of this study was not to elaborate on the usefulness of microarray analysis in general, but to expand our knowledge regarding this potential “background noise” for the widely used Illumina microarray platform surpassing existing data which focused primarily on the adult sensory and nervous system, by analyzing patterns of gene expression at different embryonic stages using wild type strains and modern transgenic models of often non-isogenic backgrounds. Results Wild type embryos of 11 mouse strains commonly used in transgenic and molecular genetic studies at three developmental time points were subjected to Illumina microarray expression profiling in a strain-by-strain comparison. Our data robustly reflects known gene expression patterns during mid-gestation development. Decreasing diversity of the input tissue and/or increasing strain diversity raised the sensitivity of the array towards the genetic background. Consistent strain sensitivity of some probes was attributed to genetic polymorphisms or probe design related artifacts. Conclusion Our study provides an extensive reference list of gene expression profiling background noise of value to anyone in the field of developmental biology and transgenic research performing microarray expression profiling with the widely used Illumina microarray platform. Probes identified as strain specific background noise further allow for microarray expression profiling on its own to be a valuable tool for establishing genealogies of mouse inbred strains. PMID:22583621

  1. Ex vivo determination of bone tissue strains for an in vivo mouse tibial loading model.

    PubMed

    Carriero, Alessandra; Abela, Lisa; Pitsillides, Andrew A; Shefelbine, Sandra J

    2014-07-18

    Previous studies introduced the digital image correlation (DIC) as a viable technique for measuring bone strain during loading. In this study, we investigated the sensitivity of a DIC system in determining surface strains in a mouse tibia while loaded in compression through the knee joint. Specifically, we examined the effect of speckle distribution, facet size and overlap, initial vertical alignment of the bone into the loading cups, rotation with respect to cameras, and ex vivo loading configurations on the strain contour maps measured with a DIC system. We loaded tibiae of C57BL/6 mice (12 and 18 weeks old male) up to 12 N at 8 N/min. Images of speckles on the bone surface were recorded at 1N intervals and DIC was used to compute strains. Results showed that speckles must have the correct size and density with respect to the facet size of choice for the strain distribution to be computed and reproducible. Initial alignment of the bone within the loading cups does not influence the strain distribution measured during peak loading, but bones must be placed in front of the camera with the same orientation in order for strains to be comparable. Finally, the ex vivo loading configurations with the tibia attached to the entire mouse, or to the femur and foot, or only to the foot, showed different strain contour maps. This work provides a better understanding of parameters affecting full field strain measurements from DIC in ex vivo murine tibial loading tests. PMID:24835472

  2. Individual strains of Lactobacillus paracasei differentially inhibit human basophil and mouse mast cell activation

    PubMed Central

    Cassard, Lydie; Lalanne, Ana Inés; Garault, Peggy; Cotillard, Aurélie; Chervaux, Christian; Wels, Michiel; Smokvina, Tamara

    2016-01-01

    Abstract Introduction The microbiota controls a variety of biological functions, including immunity, and alterations of the microbiota in early life are associated with a higher risk of developing allergies later in life. Several probiotic bacteria, and particularly lactic acid bacteria, were described to reduce both the induction of allergic responses and allergic manifestations. Although specific probiotic strains were used in these studies, their protective effects on allergic responses also might be common for all lactobacilli. Methods To determine whether allergic effector cells inhibition is a common feature of lactobacilli or whether it varies among lactobacilli strains, we compared the ability of 40 strains of the same Lactobacillus paracasei species to inhibit IgE‐dependent mouse mast cell and human basophil activation. Results We uncovered a marked heterogeneity in the inhibitory properties of the 40 Lactobacillus strains tested. These segregated into three to four clusters depending on the intensity of inhibition. Some strains inhibited both mouse mast cell and human basophil activation, others strains inhibited only one cell type and another group induced no inhibition of activation for either cell type. Conclusions Individual Lactobacillus strains of the same species differentially inhibit IgE‐dependent activation of mouse mast cells and human basophils, two cell types that are critical in the onset of allergic manifestations. Although we failed to identify specific bacterial genes associated with inhibition by gene‐trait matching analysis, our findings demonstrate the complexity of the interactions between the microbiota and the host. These results suggest that some L. paracasei strains might be more beneficial in allergies than others strains and provide the bases for a rational screening of lactic acid bacteria strains as next‐generation probiotics in the field of allergy. PMID:27621812

  3. Murine leukemia virus in organs of senescence-prone and -resistant mouse strains.

    PubMed

    Carp, R I; Meeker, H C; Chung, R; Kozak, C A; Hosokawa, M; Fujisawa, H

    2002-03-31

    A series of inbred strains of mice have been developed that are either prone (SAMP) or resistant (SAMR) to accelerated senescence. All of these strains originated from an inadvertent cross or crosses between the AKR/J mouse strain and an unknown strain(s). The characteristics of the nine senescence-prone lines differ, with all strains showing generalized aspects of accelerated aging but with each line having a specific aging-related change that is emphasized, e.g. learning and memory deficits, osteoporosis and senile amyloidosis. The senescence-resistant strains have normal patterns of aging and do not show the specific aging-related changes seen in SAMP strains. The fact that AKR mice have high levels of endogenous, ecotropic murine leukemia virus (MuLV) prompted an examination of the expression levels of MuLV in SAM strains. Analysis of brain, spleen and thymus samples revealed that seven of nine SAMP strains had high levels of MuLV and contained the Emv11 provirus (previously termed Akv1) that encodes the predominant MuLV found in AKR mice. In contrast, none of the SAMR strains had Emv11 or significant amounts of virus. The current findings represent an initial step in determining the role of MuLV in the accelerated senescence seen in SAMP strains. PMID:11850021

  4. NaCl Taste Thresholds in 13 Inbred Mouse Strains

    PubMed Central

    Ishiwatari, Yutaka

    2012-01-01

    Molecular mechanisms of salty taste in mammals are not completely understood. We use genetic approaches to study these mechanisms. Previously, we developed a high-throughput procedure to measure NaCl taste thresholds, which involves conditioning mice to avoid LiCl and then examining avoidance of NaCl solutions presented in 48-h 2-bottle preference tests. Using this procedure, we measured NaCl taste thresholds of mice from 13 genealogically divergent inbred stains: 129P3/J, A/J, BALB/cByJ, C3H/HeJ, C57BL/6ByJ, C57BL/6J, CBA/J, CE/J, DBA/2J, FVB/NJ, NZB/BlNJ, PWK/PhJ, and SJL/J. We found substantial strain variation in NaCl taste thresholds: mice from the A/J and 129P3/J strains had high thresholds (were less sensitive), whereas mice from the BALB/cByJ, C57BL/6J, C57BL/6ByJ, CE/J, DBA/2J, NZB/BINJ, and SJL/J had low thresholds (were more sensitive). NaCl taste thresholds measured in this study did not significantly correlate with NaCl preferences or amiloride sensitivity of chorda tympani nerve responses to NaCl determined in the same strains in other studies. To examine whether strain differences in NaCl taste thresholds could have been affected by variation in learning ability or sensitivity to toxic effects of LiCl, we used the same method to measure citric acid taste thresholds in 4 inbred strains with large differences in NaCl taste thresholds but similar acid sensitivity in preference tests (129P3/J, A/J, C57BL/6J, and DBA/2J). Citric acid taste thresholds were similar in these 4 strains. This suggests that our technique measures taste quality–specific thresholds that are likely to represent differences in peripheral taste responsiveness. The strain differences in NaCl taste sensitivity found in this study provide a basis for genetic analysis of this phenotype. PMID:22293936

  5. Comparative gene expression profiling in two congenic mouse strains following Bordetella pertussis infection

    PubMed Central

    Banus, Sander; Vandebriel, Rob J; Pennings, Jeroen LA; Gremmer, Eric R; Wester, Piet W; van Kranen, Henk J; Breit, Timo M; Demant, Peter; Mooi, Frits R; Hoebee, Barbara; Kimman, Tjeerd G

    2007-01-01

    Background Susceptibility to Bordetella pertussis infection varies widely. These differences can partly be explained by genetic host factors. HcB-28 mice are more resistant to B. pertussis infection than C3H mice, which could partially be ascribed to the B. pertussis susceptibility locus-1 (Bps1) on chromosome 12. The presence of C57BL/10 genome on this locus instead of C3H genome resulted in a decreased number of bacteria in the lung. To further elucidate the role of host genetic factors, in particular in the Bps1 locus, in B. pertussis infection, and to identify candidate genes within in this region, we compared expression profiles in the lungs of the C3H and HcB-28 mouse strains following B. pertussis inoculation. Twelve and a half percent of the genomes of these mice are from a different genetic background. Results Upon B. pertussis inoculation 2,353 genes were differentially expressed in the lungs of both mouse strains. Two hundred and six genes were differentially expressed between the two mouse strains, but, remarkably, none of these were up- or down-regulated upon B. pertussis infection. Of these 206 genes, 17 were located in the Bps1 region. Eight of these genes, which showed a strong difference in gene expression between the two mouse strains, map to the immunoglobulin heavy chain complex (Igh). Conclusion Gene expression changes upon B. pertussis infection are highly identical between the two mouse strains despite the differences in the course of B. pertussis infection. Because the genes that were differentially regulated between the mouse strains only showed differences in expression before infection, it appears likely that such intrinsic differences in gene regulation are involved in determining differences in susceptibility to B. pertussis infection. Alternatively, such genetic differences in susceptibility may be explained by genes that are not differentially regulated between these two mouse strains. Genes in the Igh complex, among which Igh-1a

  6. Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

    PubMed Central

    Cui, Yue; Franciszkiewicz, Katarzyna; Mburu, Yvonne K.; Mondot, Stanislas; Le Bourhis, Lionel; Premel, Virginie; Martin, Emmanuel; Kachaner, Alexandra; Duban, Livine; Ingersoll, Molly A.; Rabot, Sylvie; Jaubert, Jean; De Villartay, Jean-Pierre; Soudais, Claire; Lantz, Olivier

    2015-01-01

    Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%–10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≈0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-α locus and led to higher usage of the distal Vα segments, including Vα19. We generated a MAIThi congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+) CD4–CD8lo/neg T cells with tissue-homing properties (CCR6+CCR7–). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18Rα, and IL-12Rβ and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor γ (RORγt). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIThi congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease. PMID:26524590

  7. Genetics of Peripheral Vestibular Dysfunction: Lessons from Mutant Mouse Strains

    PubMed Central

    Jones, Sherri M.; Jones, Timothy A.

    2015-01-01

    Background A considerable amount of research has been published about genetic hearing impairment. Fifty to sixty percent of hearing loss is thought to have a genetic cause. Genes may also play a significant role in acquired hearing loss due to aging, noise exposure, or ototoxic medications. Between 1995 and 2012, over 100 causative genes have been identified for syndromic and nonsyndromic forms of hereditary hearing loss (see Hereditary Hearing Loss Homepage http://hereditaryhearingloss.org). Mouse models have been extremely valuable in facilitating the discovery of hearing loss genes, and in understanding inner ear pathology due to genetic mutations or elucidating fundamental mechanisms of inner ear development. Purpose Whereas much is being learned about hereditary hearing loss and the genetics of cochlear disorders, relatively little is known about the role genes may play in peripheral vestibular impairment. Here we review the literature with regard to genetics of vestibular dysfunction and discuss what we have learned from studies using mutant mouse models and direct measures of peripheral vestibular neural function. Results Several genes are considered that when mutated lead to varying degrees of inner ear vestibular dysfunction due to deficits in otoconia, stereocilia, hair cells, or neurons. Behavior often does not reveal the inner ear deficit. Many of the examples presented are also known to cause human disorders. Conclusions Knowledge regarding the roles of particular genes in the operation of the vestibular sensory apparatus is growing and it is clear that gene products co-expressed in the cochlea and vestibule may play different roles in the respective end organs. The discovery of new genes mediating critical inner ear vestibular function carries the promise of new strategies in diagnosing, treating and managing patients as well as predicting the course and level of morbidity in human vestibular disease. PMID:25032973

  8. GENETIC CONTROL OF SUSCEPTIBILITY TO INFECTION WITH PLASMODIUM CHABAUDI CHABAUDI AS IN INBRED MOUSE STRAINS

    PubMed Central

    Laroque, Aurélie; Min-Oo, Gundula; Tam, Mifong; Radovanovic, Irena; Stevenson, Mary M.; Gros, Philippe

    2016-01-01

    To identify genetic effects modulating blood stage replication of the malarial parasite, we phenotyped a group of 25 inbred mouse strains for susceptibility to Plasmodium chabaudi chabaudi AS infection (peak parasitemia, survival). A broad spectrum of responses was observed, with strains such as C57BL/6J being the most resistant (low parasitemia, 100% survival), and strains such as NZW/LacJ and C3HeB/FeJ being extremely susceptible (very high parasitemia and uniform lethality). A number of strains showed intermediate phenotypes and gender specific effects, suggestive of rich genetic diversity in response to malaria in inbred strains. An F2 progeny were generated from SM/J (susceptible) and C57BL/6J (resistant) parental strains, and was phenotyped for susceptibility to P. chabaudi chabaudi AS. A whole genome scan in these animals identified the Char1 locus (LOD=7.40) on chromosome 9 as a key regulator of parasite density and pointed to a conserved 0.4Mb haplotype at Char1 that segregates with susceptibility/resistance to infection. In addition, a second locus was detected in [SM/J x C57BL/6J] F2 mice on the X chromosome (LOD=4.26), which was given the temporary designation Char11. These studies identify a conserved role of Char1 in regulating response to malaria in inbred mouse strains, and provide a prioritized 0.4Mb interval for the search of positional candidates. PMID:21975430

  9. Susceptibility to quantum dot induced lung inflammation differs widely among the Collaborative Cross founder mouse strains.

    PubMed

    Scoville, David K; White, Collin C; Botta, Dianne; McConnachie, Lisa A; Zadworny, Megan E; Schmuck, Stefanie C; Hu, Xiaoge; Gao, Xiaohu; Yu, Jianbo; Dills, Russell L; Sheppard, Lianne; Delaney, Martha A; Griffith, William C; Beyer, Richard P; Zangar, Richard C; Pounds, Joel G; Faustman, Elaine M; Kavanagh, Terrance J

    2015-12-01

    Quantum dots (QDs) are engineered semiconductor nanoparticles with unique physicochemical properties that make them potentially useful in clinical, research and industrial settings. However, a growing body of evidence indicates that like other engineered nanomaterials, QDs have the potential to be respiratory hazards, especially in the context of the manufacture of QDs and products containing them, as well as exposures to consumers using these products. The overall goal of this study was to investigate the role of mouse strain in determining susceptibility to QD-induced pulmonary inflammation and toxicity. Male mice from 8 genetically diverse inbred strains (the Collaborative Cross founder strains) were exposed to CdSe-ZnS core-shell QDs stabilized with an amphiphilic polymer. QD treatment resulted in significant increases in the percentage of neutrophils and levels of cytokines present in bronchoalveolar lavage fluid (BALF) obtained from NOD/ShiLtJ and NZO/HlLtJ mice relative to their saline (Sal) treated controls. Cadmium measurements in lung tissue indicated strain-dependent differences in disposition of QDs in the lung. Total glutathione levels in lung tissue were significantly correlated with percent neutrophils in BALF as well as with lung tissue Cd levels. Our findings indicate that QD-induced acute lung inflammation is mouse strain dependent, that it is heritable, and that the choice of mouse strain is an important consideration in planning QD toxicity studies. These data also suggest that formal genetic analyses using additional strains or recombinant inbred strains from these mice could be useful for discovering potential QD-induced inflammation susceptibility loci. PMID:26476918

  10. Purification by expanded bed adsorption and characterization of an alpha-amylases FORILASE NTL from A. niger.

    PubMed

    Toledo, A L; Severo, J B; Souza, R R; Campos, E S; Santana, J C C; Tambourgi, E B

    2007-02-01

    In this work the purification and biochemistry characterization of alpha-amylases from Aspergillus niger (FORILASE NTL) were studied. The effects of expansion degree of resin bed on enzyme purification by expanded bed adsorption (EBA) have also been studied. Residence time distributions (RTD) studies were done to achieve the optimal conditions of the amylases recovery on ion-exchange resin, and glucose solution was used as a new tracer. Results showed that height equivalent of the theoretical plates (HETP), axial dispersion and the Prandt number increased with bed height, bed voidage and linear velocity. The adsorption capacity of alpha-amylases, on the resin, increased with bed height and the best condition was at four-expansion degree. alpha-Amylase characterization showed that this enzyme has high affinity with soluble starch, good hydrolysis potential and molecular weight of 116 kDa. PMID:16959553

  11. Bifidobacteria modulate cognitive processes in an anxious mouse strain.

    PubMed

    Savignac, H M; Tramullas, M; Kiely, B; Dinan, T G; Cryan, J F

    2015-01-01

    Increasing evidence suggests that a brain-gut-microbiome axis exists, which has the potential to play a major role in modulating behaviour. However, the role of this axis in cognition remains relatively unexplored. Probiotics, which are commensal bacteria offering potential health benefit, have been shown to decrease anxiety, depression and visceral pain-related behaviours. In this study, we investigate the potential of two Bifidobacteria strains to modulate cognitive processes and visceral pain sensitivity. Adult male BALB/c mice were fed daily for 11 weeks with B. longum 1714, B. breve 1205 or vehicle treatment. Starting at week 4, animals were behaviourally assessed in a battery of tests relevant to different aspects of cognition, as well as locomotor activity and visceral pain. In the object recognition test, B. longum 1714-fed mice discriminated between the two objects faster than all other groups and B. breve 1205-fed mice discriminated faster than vehicle animals. In the Barnes maze, B. longum 1714-treated mice made fewer errors than other groups, suggesting a better learning. In the fear conditioning, B. longum 1714-treated group also showed better learning and memory, yet presenting the same extinction learning profile as controls. None of the treatments affected visceral sensitivity. Altogether, these data suggest that B. longum 1714 had a positive impact on cognition and also that the effects of individual Bifidobacteria strains do not generalise across the species. Clinical validation of the effects of probiotics on cognition is now warranted. PMID:25794930

  12. The effect of dam strain on the craniofacial morphogenesis of CL/Fr mouse fetuses.

    PubMed

    Martin, D A; Nonaka, K; Yanagita, K; Nakata, M

    1995-01-01

    The embryo transfer technique and cephalometry were used to investigate the effect of dam strain in intrauterine craniofacial growth and the severity of cleft lip and palate (CLP) in a CLP-susceptible CL/Fr strain of embryos. The CL/Fr strain of embryos at early blastocyst stage was transferred to the same dam strain and to the CLP-resistant C57BL dam strain. On the 18th gestational day, each dam was laparotomized to take out the fetuses. The spontaneous incidence of CLP in the fetuses was checked and a cephalometric observation of the craniofacial complex of each fetus was done just after laparotomy. The dorsoventral craniofacial size of the unaffected fetuses and the severity of CLP i the affected ones were compared between both dam strains. The following results were obtained: 1) The overall craniofacial sizes of the unaffected fetuses observed in the CL/Fr dam strain were significantly smaller than those seen in the C57/BL dam strain. Those of the affected fetuses observed in the CL/Fr dam strain were smaller than those seen in the C57BL dam strain although the interstrain difference was not significant. 20 The dam strain had a highly significant effect on the craniofacial size of the unaffected fetuses. 3) The CLP frequency in the CL/Fr dam strain was significantly higher than that in the C57BL dam strain. 4) The severity of CLP in the affected fetuses observed in the CL/Fr dam strain was significantly more serious than that seen in the C57BL dam strain. These results indicated that the CLP-susceptible CL/Fr dam strain retarded the intrauterine craniofacial growth of the fetuses and that the cleft condition in the affected fetuses observed in the CL/Fr dam strain was more seriously affected than that seen in the CLP-resistant C57BL dam strain. Thus, it can be concluded that the effect of the dam strain played an important role in the craniofacial morphogenesis of the CL/Fr strain of mouse fetuses that developed from the embryo transferred to the CL/Fr and C57

  13. Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains.

    PubMed

    Wiltshire, T; Ervin, R B; Duan, H; Bogue, M A; Zamboni, W C; Cook, S; Chung, W; Zou, F; Tarantino, L M

    2015-03-01

    Initial sensitivity to psychostimulants can predict subsequent use and abuse in humans. Acute locomotor activation in response to psychostimulants is commonly used as an animal model of initial drug sensitivity and has been shown to have a substantial genetic component. Identifying the specific genetic differences that lead to phenotypic differences in initial drug sensitivity can advance our understanding of the processes that lead to addiction. Phenotyping inbred mouse strain panels are frequently used as a first step for studying the genetic architecture of complex traits. We assessed locomotor activation following a single, acute 20 mg/kg dose of cocaine (COC) in males from 45 inbred mouse strains and observed significant phenotypic variation across strains indicating a substantial genetic component. We also measured levels of COC, the active metabolite, norcocaine and the major inactive metabolite, benzoylecgonine, in plasma and brain in the same set of inbred strains. Pharmacokinetic (PK) and behavioral data were significantly correlated, but at a level that indicates that PK alone does not account for the behavioral differences observed across strains. Phenotypic data from this reference population of inbred strains can be utilized in studies aimed at examining the role of psychostimulant-induced locomotor activation on drug reward and reinforcement and to test theories about addiction processes. Moreover, these data serve as a starting point for identifying genes that alter sensitivity to the locomotor stimulatory effects of COC. PMID:25727211

  14. Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains

    PubMed Central

    Wiltshire, T.; Ervin, R. B.; Duan, H.; Bogue, M. A.; Zamboni, W. C.; Cook, S.; Chung, W.; Zou, F.; Tarantino, L. M.

    2015-01-01

    Initial sensitivity to psychostimulants can predict subsequent use and abuse in humans. Acute locomotor activation in response to psychostimulants is commonly used as an animal model of initial drug sensitivity and has been shown to have a substantial genetic component. Identifying the specific genetic differences that lead to phenotypic differences in initial drug sensitivity can advance our understanding of the processes that lead to addiction. Phenotyping inbred mouse strain panels are frequently used as a first step for studying the genetic architecture of complex traits. We assessed locomotor activation following a single, acute 20 mg/kg dose of cocaine (COC) in males from 45 inbred mouse strains and observed significant phenotypic variation across strains indicating a substantial genetic component. We also measured levels of COC, the active metabolite, norcocaine and the major inactive metabolite, benzoylecgonine, in plasma and brain in the same set of inbred strains. Pharmacokinetic (PK) and behavioral data were significantly correlated, but at a level that indicates that PK alone does not account for the behavioral differences observed across strains. Phenotypic data from this reference population of inbred strains can be utilized in studies aimed at examining the role of psychostimulant-induced locomotor activation on drug reward and reinforcement and to test theories about addiction processes. Moreover, these data serve as a starting point for identifying genes that alter sensitivity to the locomotor stimulatory effects of COC. PMID:25727211

  15. Mouse consomic strains: Exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies

    PubMed Central

    Gregorová, Sona; Divina, Petr; Storchova, Radka; Trachtulec, Zdenek; Fotopulosova, Vladana; Svenson, Karen L.; Donahue, Leah Rae; Paigen, Beverly; Forejt, Jiri

    2008-01-01

    Consomic (chromosome substitution) strains (CSs) represent the most recent addition to the mouse genetic resources aimed to geneticaly analyze complex trait loci (QTLs). In this study, we report the development of a set of 28 mouse intersubspecific CSs. In each CS, we replaced a single chromosome of the C57BL/6J (B6) inbred strain (mostly Mus m. domesticus) with its homolog from the PWD/Ph inbred strain of the Mus m. musculus subspecies. These two progenitor subspecies diverged less than 1 million years ago and accumulated a large number of genetic differences that constitute a rich resource of genetic variation for QTL analyses. Altogether, the 18 consomic, nine subconsomic, and one conplastic strain covered all 19 autosomes, X and Y sex chromosomes, and mitochondrial DNA. Most CSs had significantly lower reproductive fitness compared with the progenitor strains. CSs homosomic for chromosomes 10 and 11, and the C57BL/6J-Chr X males, failed to reproduce and were substituted by less affected subconsomics carrying either a proximal, central, or distal part of the respective chromosome. A genome-wide scan of 965 DNA markers revealed 99.87% purity of the B6 genetic background. Thirty-three nonsynonymous substitutions were uncovered in the protein-coding regions of the mitochondrial DNA of the B6.PWD-mt conplastic strain. A pilot-phenotyping experiment project revealed a high number of variations among B6.PWD consomics. PMID:18256238

  16. IMMUNE-DEFICIENT MOUSE STRAINS DISPLAY MARKED VARIABILITY IN GROWTH OF HUMAN MELANOMA LUNG METASTASES

    PubMed Central

    Carreno, Beatriz M.; Garbow, Joel R.; Kolar, Grant R.; Jackson, Erin N.; Engelbach, John A.; Becker-Hapak, Michelle; Carayannopoulos, Leonidas N.; Piwnica-Worms, David; Linette, Gerald P.

    2009-01-01

    Purpose Immune-deficient mice serve as critical hosts for transplantation of xenogeneic cells for in vivo analysis of various biological processes. Since investigators typically select one or two immune-deficient mouse strains as recipients, no comprehensive study has been published documenting differences in human tumor engraftment. Taking advantage of the increased metastatic potential of RhoC-expressing human (A375) melanoma cells, we evaluate 4 immune-deficient mouse strains: scid, NOD-scid, NOD-scid β2mnull, and NOD-scid IL2Rγnull as xenograft tumor recipients. Experimental design Bioluminescence, magnetic resonance imaging and histopathology was employed to monitor serial tumor growth. NK cell function was examined in each mouse strain using standard 51 Chromium release assays. Results Melanoma metastases growth is delayed and variable in scid, and NOD-scid mice. In contrast, NOD-scid β2mnull and NOD-scid IL2Rγnull mice show rapid tumor engraftment, although tumor growth is variable in NOD-scid β2mnull mice. NK cells were detected in all strains except NOD-scid IL2Rγnull, and in vitro activated scid, NOD-scid and NOD-scid β2mnull NK cells kill human melanoma lines and primary melanoma cells. Expression of human NKG2D ligands MHC class I chain-related A and B molecules renders melanoma susceptible to murine NK cell-mediated cytotoxicity and killing is inhibited by antibody blockade of murine NKG2D. Conclusions Murine NKG2D recognition of MICA/B is an important receptor-ligand interaction employed by NK cells in immune-deficient strains to limit engraftment of human tumors. The absolute NK deficiency in NOD-scid IL2Rγnull animals makes this strain an excellent recipient of melanoma and potentially other human malignancies. PMID:19447870

  17. Photoreceptor degeneration and rd1 mutation in the grizzled/mocha mouse strain.

    PubMed

    Qiao, Xiaoxi; Pennesi, Mark; Seong, Eunju; Gao, Hua; Burmeister, Margit; Wu, Samuel M

    2003-04-01

    The mocha mouse is a spontaneous mutant carrying a defective adaptor-like protein complex AP-3delta subunit. We examined retinal function and histology of the mocha mutant. We found that not only mocha homozygotes but also other littermates in the inbred strain are blind due to severe defects in both rod and cone photoreceptors on electroretinogram recordings. The functional deficit was caused by rapid, early postnatal photoreceptor degeneration. Genotyping confirmed the presence of a viral insertion of rd1 gene in the mocha strain. We conclude that rd1 allele contamination is primarily responsible for photoreceptor degeneration, and caution against behavioral tests with visual cues in the present stocks. PMID:12668055

  18. Differences in saccharin preference and genetic alterations of the Tas1r3 gene among senescence-accelerated mouse strains and their parental AKR/J strain.

    PubMed

    Niimi, Kimie; Takahashi, Eiki

    2014-05-10

    The senescence-accelerated mouse (SAM) is used as an animal model of senescence acceleration and age-associated disorders. SAM is derived from unexpected crosses between the AKR/J and unknown mouse strains. There are nine senescence-prone (SAMP) strains and three senescence-resistant (SAMR) strains. Although SAMP strains exhibit strain-specific and age-related pathological changes, the genes responsible for the pathologic changes in SAMP strains have not been comprehensively identified. In the present study, we evaluated sweet taste perception using the two-bottle test. We compared genotypes of the taste related gene, Tas1r3, using SAM strains and the parental AKR/J strain. The two-bottle test revealed that SAMR1 (R1), SAMP6 (P6), SAMP8 (P8), and SAMP10 (P10) mice were saccharin-preferring strains, whereas AKR/J did not prefer saccharin. All genotypes of the R1, P6, P8, and P10 strains at the polymorphic sites in Tas1r3, which is known to influence saccharin preference, were identical to those of C57BL6/J, a well-known saccharin-preferring strain, and were completely different from those of the parental AKR/J strain. These genetic alterations in SAM strains appear to arise from an unknown strain that is thought to have been crossed with AKR/J initially. PMID:24726396

  19. Metabolism of human cytochrome P450 marker substrates in mouse: a strain and gender comparison.

    PubMed

    Löfgren, S; Hagbjörk, A L; Ekman, S; Fransson-Steen, R; Terelius, Y

    2004-09-01

    The aim was to characterize mouse gender and strain differences in the metabolism of commonly used human cytochrome (CYP) P450 probe substrates. Thirteen human CYP probe substrates (phenacetin, coumarin, 7-ethoxy-4-trifluoromethyl coumarin, amiodarone, paclitaxel, diclofenac, S-mephenytoin, bufuralol, dextromethorphan, chlorzoxazone, p-nitrophenol, testosterone and lauric acid) were used in activity measurements. The metabolism of the probe substrates was compared in liver microsomes from male and female NMRI, CBA, C57bl/6, 129/SvJ and CD1 strains. The expression of proteins identified on Western blots with commonly available antibodies selective for specific human and rat CYP enzymes were compared in the different mouse strains. Males had higher metabolism than corresponding females for phenacetin O-deethylation (human marker for CYP1A2 activity), and a high correlation was found between phenacetin activity and immunoreactivity in Western blots produced with rat CYP1A2 antibodies. Protein detected by antibodies cross-reacting with human CYP2B6 and rat CYP2B1/2 antibodies was female specific except for the 129/SvJ strain, where it was absent in both genders. Females generally had a higher metabolism of bufuralol 1'-hydroxylation and dextromethorphan O-demethylation (human markers for CYP2D activity). Bufuralol 1'-hydroxylation correlated with a female-dominant mouse CYP, which was detected with antibodies against rat CYP2D4. p-Nitrophenol 2-hydroxylation correlated better than chlorzoxazone 6-hydroxylation with the protein detected with antibodies against rat CYP2E1, indicating that p-nitrophenol is a more specific substrate for mouse CYP2E1. PMID:15742976

  20. Brain immune cell composition and functional outcome after cerebral ischemia: comparison of two mouse strains

    PubMed Central

    Kim, Hyun Ah; Whittle, Stephanie C.; Lee, Seyoung; Chu, Hannah X.; Zhang, Shenpeng R.; Wei, Zihui; Arumugam, Thiruma V.; Vinh, Anthony; Drummond, Grant R.; Sobey, Christopher G.

    2014-01-01

    Inflammatory cells may contribute to secondary brain injury following cerebral ischemia. The C57Bl/6 mouse strain is known to exhibit a T helper 1-prone, pro-inflammatory type response to injury, whereas the FVB strain is relatively T helper 2-prone, or anti-inflammatory, in its immune response. We tested whether stroke outcome is more severe in C57Bl/6 than FVB mice. Male mice of each strain underwent sham surgery or 1 h occlusion of the middle cerebral artery followed by 23 h of reperfusion. Despite no difference in infarct size, C57Bl/6 mice displayed markedly greater functional deficits than FVB mice after stroke, as assessed by neurological scoring and hanging wire test. Total numbers of CD45+ leukocytes tended to be larger in the brains of C57Bl/6 than FVB mice after stroke, but there were marked differences in leukocyte composition between the two mouse strains. The inflammatory response in C57Bl/6 mice primarily involved T and B lymphocytes, whereas neutrophils, monocytes and macrophages were more prominent in FVB mice. Our data are consistent with the concept that functional outcome after stroke is dependent on the immune cell composition which develops following ischemic brain injury. PMID:25477780

  1. Expression of murine leukemia viruses in the highly lymphomatous BXH-2 recombinant inbred mouse strain.

    PubMed Central

    Bedigian, H G; Taylor, B A; Meier, H

    1981-01-01

    Among 12 recombinant inbred strains of mice derived from crossing two strains, C57BL/6J and C3H/HeJ, which have a low incidence of neoplastic disease, one strain (BXH-2) has been found to have a high incidence of lymphoma, of non-T-cell origin, at an early age. The BXH-2 strain carries the Fv-1b allele and spontaneously expresses a B-tropic murine leukemia virus beginning at as early as 10 days of gestation and continuing throughout their life. No significant differences in ecotropic virus titers were observed at any age tested (16 to 17 days of gestation through 7 months), whereas xenotropic virus was first detected in lymphoid tissues of 2-month-old mice and virus titers increased with age. Dual tropic virus(es), which induced cytopathic changes on mink lung cells, was isolated from BXH-2 lymphomatous tissues. Unlike AKR mink lung focus-forming virus (N-tropic recombinant), BXH-2 dual tropic virus is B tropic and induces cytopathic changes in mouse fibroblast cultures as well. The BXH-2 mouse provides a model system for studying the role of replication-competent viruses in spontaneously occurring leukemias of non-T-cell lineage and neurological disease. Images PMID:6268848

  2. Immune Competency of a Hairless Mouse Strain for Improved Preclinical Studies in Genetically-Engineered Mice

    PubMed Central

    Schaffer, Beverly S.; Grayson, Marcia H.; Wortham, Joy M.; Kubicek, Courtney B.; McCleish, Amanda T.; Prajapati, Suresh I.; Nelon, Laura D.; Brady, Michelle M.; Jung, Inkyung; Hosoyama, Tohru; Sarro, Leslea M.; Hanes, Martha A.; Rubin, Brian P.; Michalek, Joel E.; Clifford, Charles B.; Infante, Anthony J.; Keller, Charles

    2010-01-01

    Genetically-engineered mouse models (GEMMs) of cancer are of increasing value to preclinical therapeutics. Optical imaging is a cost-effective method of assessing deep-seated tumor growth in GEMMs whose tumors can be encoded to express luminescent or fluorescent reporters, although reporter signal attenuation would be improved if animals were fur-free. In this study, we sought to determine whether hereditable furlessness resulting from a hypomorphic mutation in the Hairless gene would or would not also affect immune competence. By assessment of humoral and cellular immunity of the SKH1 mouse line bearing the hypomorphic Hairless mutation, we determined that blood counts, immunoglobulin levels, and CD4+ and CD8+ T cells were comparable between SKH1 and the C57Bl/6 strain. On examination of T cell subsets, statistically significant differences in naïve T cells (1.7 vs. 3.4 × 105 cells/spleen in SKH1 vs. C57Bl/6, p=0.008) and memory T cells (1.4 vs. 0.13 × 106 cells/spleen in SKH1 vs. C57Bl/6, p=0.008) were detected. However, the numerical differences did not result in altered T cell functional response to antigen re-challenge (keyhole limpet hemocyanin) in a lymph node cell in vitro proliferative assay. Furthermore, interbreeding the SKH1 mouse line to a rhabdomyosarcoma GEMM demonstrated preserved anti-tumor responses of CD56+ Natural Killer cells and CD163+ macrophages, without any differences in tumor pathology. The fur-free GEMM was also especially amenable to multiplex optical imaging. Thus, SKH1 represents an immune competent, fur-free mouse strain which may be of use for interbreeding to other genetically-engineered mouse models of cancer for improved preclinical studies. PMID:20663932

  3. Psychomotor stimulant effects of cocaine in rats and 15 mouse strains

    PubMed Central

    Thomsen, Morgane; Caine, S. Barak

    2012-01-01

    Relative to intravenous drug self-administration, locomotor activity is easier to measure with high throughput, particularly in mice. Therefore its potential to predict differences in self-administration between genotypes (e.g., targeted mutations, recombinant inbred strains) is appealing, but such predictive value is unverified. The main goal of this study was to evaluate the utility of the locomotor assay for accurately predicting differences in cocaine self-administration. A second goal was to evaluate any correlation between activity in a novel environment, and cocaine-induced hyperactivity, between strains. We evaluated locomotor activity in male and female Sprague-Dawley rats and 15 mouse strains (129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ, A/J, BALB/cByJ, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, and outbred Swiss Webster and CD-1/ICR), as well as cocaine self-administration in BALB substrains. All but BALB/cJ mice showed locomotor habituation and significant cocaine-induced hyperactivity. BALB/cJ mice also failed to self-administer cocaine. BALB/cByJ mice showed modest locomotor habituation, cocaine-induced locomotion, and cocaine self-administration. As previously reported, female rats showed greater cocaine-induced locomotion than males, but this was only observed in one of fifteen mouse strains (FVB/NJ), and the reverse was observed in two strains (129X1/SvJ, BALB/cByJ). The intriguing phenotype of the BALB/cJ strain may indicate some correlation between all-or-none locomotion in a novel environment, and stimulant and reinforcing effects of cocaine. However, neither novelty- nor cocaine-induced activity offered a clear prediction of relative reinforcing effects among strains. Additionally, these results should aid in selecting mouse strains for future studies in which relative locomotor responsiveness to psychostimulants is a necessary consideration. PMID:21843010

  4. Mitochondrial DNA and Functional Investigations into the Radiosensitivity of Four Mouse Strains

    PubMed Central

    Zhang, Steven B.; Maguire, David; Zhang, Mei; Tian, Yeping; Yang, Shanmin; Zhang, Amy; Casey-Sawicki, Katherine; Han, Deping; Ma, Jun; Yin, Liangjie; Guo, Yongson; Wang, Xiaohui; Chen, Chun; Litvinchuk, Alexandra; Zhang, Zhenhuan; Swarts, Steven; Vidyasagar, Sadasivan; Zhang, Lurong; Okunieff, Paul

    2014-01-01

    We investigated whether genetic radiosensitivity-related changes in mtDNA/nDNA ratios are significant to mitochondrial function and if a material effect on mtDNA content and function exists. BALB/c (radiosensitive), C57BL/6 (radioresistant), and F1 hybrid mouse strains were exposed to total body irradiation. Hepatic genomic DNA was extracted, and mitochondria were isolated. Mitochondrial oxygen consumption, ROS, and calcium-induced mitochondrial swelling were measured. Radiation influenced strain-specific survival in vivo. F1 hybrid survival was influenced by maternal input. Changes in mitochondrial content corresponded to survival in vivo among the 4 strains. Calcium-induced mitochondrial swelling was strain dependent. Isolated mitochondria from BALB/c mice were significantly more sensitive to calcium overload than mitochondria from C57BL/6 mice. Maternal input partially influenced the recovery effect of radiation on calcium-induced mitochondrial swelling in F1 hybrids; the hybrid with a radiosensitive maternal lineage exhibited a lower rate of recovery. Hybrids had a survival rate that was biased toward maternal input. mtDNA content and mitochondrial permeability transition pores (MPTP) measured in these strains before irradiation reflected a dominant input from the parent. After irradiation, the MPTP opened sooner in radiosensitive and hybrid strains, likely triggering intrinsic apoptotic pathways. These findings have important implications for translation into predictors of radiation sensitivity/resistance. PMID:24688546

  5. NTL9 Folding at Constant pH: The Importance of Electrostatic Interaction and pH Dependence.

    PubMed

    Contessoto, Vinícius G; de Oliveira, Vinícius M; de Carvalho, Sidney J; Oliveira, Leandro C; Leite, Vitor B P

    2016-07-12

    The folding process of the N-terminal domain of ribosomal protein L9 (NTL9) was investigated at constant-pH computer simulations. Evaluation of the role of electrostatic interaction during folding was carried out by including a Debye-Hückel potential into a Cα structure-based model (SBM). In this study, the charges of the ionizable residues and the electrostatic potential are susceptible to the solution conditions, such as pH and ionic strength, as well as to the presence of charged groups. Simulations were performed under different pHs, and the results were validated by comparing them with experimental values of pKa and with denaturation experiment data. Also, the free energy profiles, Φ-values, and folding routes were calculated for each condition. It was shown how charges vary along the folding under different pH, which is subject to different scenarios. This study reveals how simplified models can capture essential physical features, reproducing experimental results, and presenting the role of electrostatic interactions before, during, and after the transition state. PMID:27327651

  6. SENCAR mouse skin tumorigenesis model versus other strains and stocks of mice

    SciTech Connect

    Slaga, T.J.

    1986-09-01

    The SENCAR mouse stock was selectively bred for eight generations for sensitivity to skin tumor induction by the two-stage tumorigenesis protocol using 7,12-dimethylbenz(a)anthracene (DMBA) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The SENCAR mouse was derived by crossing Charles River CD-1 mice with skin-tumor-sensitive mice (STS). The SENCAR mice are much more sensitive to both DMBA tumor initiation and TPA tumor promotion than CD-1, BALB/c, and DBA/2 mice. An even greater difference in the sensitivity to two-stage skin tumorigenesis is apparent between SENCAR and C57BL/6 mice when using DMBA-TPA treatment. However, the SENCAR and C57BL/6 mice have a similar tumor response to DMBA-benzoyl peroxide treatment, suggesting that TPA is not an effective promoter in C57BL/6 mice. The DBA/2 mice respond in a similar manner to the SENCAR mice when using N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-TPA treatment. The SENCAR mouse model provides a good dose-response relationship for many carcinogens used as tumor initiators and for many compounds used as tumor promoter. When compared to other stocks and strains of mice, the SENCAR mouse has one of the largest data bases for carcinogens and promoters.

  7. The NASA Tournament Laboratory (NTL): Improving Data Access at PDS while Spreading Joy and Engaging Students through 16 Micro-Contests

    NASA Technical Reports Server (NTRS)

    LaMora, Andy; Raugh, A.; Erickson, K.; Grayzeck, E. J.; Knopf, W.; Morgan, T. H.

    2012-01-01

    NASA PDS hosts terabytes of valuable data from hundreds of data sources and spans decades of research. Data is stored on flat-file systems regulated through careful meta dictionaries. PDS's data is available to the public through its website which supports data searches through drill-down navigation. While the system returns data quickly, result sets in response to identical input differ depending on the drill-down path a user follows. To correct this Issue, to allow custom searching, and to improve general accessibility, PDS sought to create a new data structure and API, and to use them to build applications that are a joy to use and showcase the value of the data to students, teachers and citizens. PDS engaged TopCoder and Harvard Business School through the NTL to pursue these objectives in a pilot effort. Scope was limited to Small Bodies Node data. NTL analyzed data, proposed a solution, and implemented it through a series of micro-contests. Contest focused on different segments of the problem; conceptualization, architectural design, implementation, testing, etc. To demonstrate the utility of the completed solution, NTL developed web-based and mobile applications that can compare targets, regardless of mission. To further explore the potential of the solution NTL hosted "Mash-up" challenges that integrated the API with other publically available assets, to produce consumer and teaching applications, including an Augmented Reality iPad tool. Two contests were also posted to middle and high school students via the NoNameSite.com platform, and as a result of these contests, PDS/SBN has initiated a Facebook program. These contests defined and implemented a data warehouse with the necessary migration tools to transform legacy data, produced a public web interface for the new search, developed a public API, and produced four mobile applications that we expect to appeal to users both within and, without the academic community.

  8. Differential visual system organization and susceptibility to experimental models of optic neuropathies in three commonly used mouse strains.

    PubMed

    De Groef, Lies; Dekeyster, Eline; Geeraerts, Emiel; Lefevere, Evy; Stalmans, Ingeborg; Salinas-Navarro, Manuel; Moons, Lieve

    2016-04-01

    Mouse disease models have proven indispensable in glaucoma research, yet the complexity of the vast number of models and mouse strains has also led to confusing findings. In this study, we evaluated baseline intraocular pressure, retinal histology, and retinofugal projections in three mouse strains commonly used in glaucoma research, i.e. C57Bl/6, C57Bl/6-Tyr(c), and CD-1 mice. We found that the mouse strains under study do not only display moderate variations in their intraocular pressure, retinal architecture, and retinal ganglion cell density, also the retinofugal projections to the dorsal lateral geniculate nucleus and the superior colliculus revealed striking differences, potentially underlying diverging optokinetic tracking responses and visual acuity. Next, we reviewed the success rate of three models of (glaucomatous) optic neuropathies (intravitreal N-methyl-d-aspartic acid injection, optic nerve crush, and laser photocoagulation-induced ocular hypertension), looking for differences in disease susceptibility between these mouse strains. Different genetic backgrounds and albinism led to differential susceptibility to experimentally induced retinal ganglion cell death among these three mouse strains. Overall, CD-1 mice appeared to have the highest sensitivity to retinal ganglion cell damage, while the C57Bl/6 background was more resistant in the three models used. PMID:26791081

  9. Differential effects of sucrose and fructose on dietary obesity in four mouse strains

    PubMed Central

    Glendinnning, John I.; Breinager, Lindsey; Kyrillou, Emily; Lacuna, Kristine; Rocha, Rotsen; Sclafani, Anthony

    2010-01-01

    We examined sugar-induced obesity in mouse strains polymorphic for Tas1r3, a gene that codes for the T1R3 sugar taste receptor. The T1R3 receptor in the FVB and B6 strains has a higher affinity for sugars than that in the AKR and 129P3 strains. In Experiment 1, mice had 40 days of access to lab chow plus water, sucrose (10 or 34%), or fructose (10 or 34%) solutions. The strains consumed more of the sucrose than isocaloric fructose solutions. The pattern of strain differences in caloric intake from the 10% sugar solutions was FVB > 129P3 = B6 > AKR; and that from the 34% sugar solutions was FVB > 129P3 > B6 ≥ AKR. Despite consuming more sugar calories, the FVB mice resisted obesity altogether. The AKR and 129P3 mice became obese exclusively on the 34% sucrose diet, while the B6 mice did so on the 34% sucrose and 34% fructose diets. In Experiment 2, we compared total caloric intake from diets containing chow versus chow plus 34% sucrose. All strains consumed 15-29% more calories from the sucrose-supplemented diet. In Experiment 3, we compared the oral acceptability of the sucrose and fructose solutions, using lick tests. All strains licked more avidly for the 10% sucrose solutions. The results indicate that in mice (a) Tas1r3 genotype does not predict sugar-induced hyperphagia or obesity; (b) sucrose solutions stimulate higher daily intakes than isocaloric fructose solutions; and (c) susceptibility to sugar-induced obesity varies with strain, sugar concentration and sugar type. PMID:20600198

  10. Comparative analysis of the behavioral and biomolecular parameters of four mouse strains.

    PubMed

    Nesher, Elimelech; Peskov, Vladimir; Rylova, Anna; Raz, Olga; Pinhasov, Albert

    2012-02-01

    The use of mice as experimental models in pharmacological and biochemical research began over 100 years ago, during which time different mice strains with specific features were developed. Numerous studies demonstrate that the pharmacological efficacy of various compounds significantly varies among different animal strains, a factor which must be considered when analyzing experimental data. The Sabra strain, developed more than 35 years ago, is widely used for research in Israel but has an unclear origin and is not characterized as well as other strains. Comparative analyses of the molecular characteristics of Sabra and other strains should help to understand their characteristics and to enhance the validity of their experimental use. Thus, four mouse strains-outbred ICR and Sabra as well as inbred C57Bl/6J and Balb/c were compared. Animals' weight, blood corticosterone and hippocampal BDNF mRNA levels were measured, and animals' behavior was compared using the EPM, open field, FST, and hot plate tests. We found that although Sabra mice are bigger and heavier than other tested lines, this is not reflected in behavior or in biomolecular features, wherein Sabra mice lay within the diapason of other tested animals. Thus, behavioral tests of anxiety-like behavior and locomotor activity revealed that Sabra mice scored close to the mean of all tested lines. Analysis of blood corticosterone levels did not show significant differences among tested strains. We also found a correlation between general and locomotor activity of the tested strains and their hippocampal BDNF mRNA expression. In summary, we may conclude that Sabra mice have traits similar to the better known lines, and therefore they are good subjects for neuroscience research. PMID:21598024

  11. CYCLOPENTA-FUSED POLYCYCLIC AROMATIC HYDROCARBONS IN STRAIN A/J MOUSE LUNG: DNA ADDUCTS, ONCOGENE MUTATIONS, & TUMORIGENESIS

    EPA Science Inventory

    Cyclopenta-fused Polycyclic Aromatic Hydrocarbons in Strain AJJ Mouse Lung: DNA Adducts, Oncogene Mutations, and Tumorigenesis.

    We have examined the relationships between DNA adducts, Ki-ras oncogene mutations, DNA adducts, and adenoma induction in the lungs of strain A/J...

  12. Effects of Varied Housing Density on a Hybrid Mouse Strain Followed for 20 Months.

    PubMed

    Paigen, Beverly; Currer, Joanne M; Svenson, Karen L

    2016-01-01

    To evaluate the effect of increased housing density in a hybrid mouse strain, we evaluated a panel of physiological and behavioral traits in animals that were housed in groups of 3, 5, 8, or 12, using cages that provide 78.1 in2 of floor space. Such groupings resulted in cage densities that ranged from half to almost twice the density recommended by the Guide for the Care and Use of Laboratory Animals. While previous studies have investigated physiological effects of increased housing density using inbred mouse strains, including C57BL/6J and 129S1/SvImJ, this study tested an F1 hybrid population of C57BL/6J x 129S1/SvImJ for changes resulting from either decreased or increased housing density. Mice were followed until they were 20 months old, a substantially longer duration than has been used in previous density studies. We evaluated mortality, growth, home cage behavior, blood pressure, body composition, clinical plasma chemistries, immune function, and organ weights (heart, kidney, adrenal glands, and testes) as endpoints of chronic stress that may arise from sub-optimal housing conditions. Few statistically different parameters were observed in this study, none of which describe chronic stress and all within normal physiological ranges for research mice, suggesting that this hybrid strain was not adversely affected by housing at twice the density currently recommended. PMID:26900840

  13. Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function.

    PubMed

    Berry, Daniel C; Jiang, Yuwei; Graff, Jonathan M

    2016-01-01

    Cold temperatures induce formation of beige adipocytes, which convert glucose and fatty acids to heat, and may increase energy expenditure, reduce adiposity and lower blood glucose. This therapeutic potential is unrealized, hindered by a dearth of genetic tools to fate map, track and manipulate beige progenitors and 'beiging'. Here we examined 12 Cre/inducible Cre mouse strains that mark adipocyte, muscle and mural lineages, three proposed beige origins. Among these mouse strains, only those that marked perivascular mural cells tracked the cold-induced beige lineage. Two SMA-based strains, SMA-Cre(ERT2) and SMA-rtTA, fate mapped into the majority of cold-induced beige adipocytes and SMA-marked progenitors appeared essential for beiging. Disruption of the potential of the SMA-tracked progenitors to form beige adipocytes was accompanied by an inability to maintain body temperature and by hyperglycaemia. Thus, SMA-engineered mice may be useful to track and manipulate beige progenitors, beige adipocyte formation and function. PMID:26729601

  14. High-Density Genotypes of Inbred Mouse Strains: Improved Power and Precision of Association Mapping

    PubMed Central

    Rau, Christoph D.; Parks, Brian; Wang, Yibin; Eskin, Eleazar; Simecek, Petr; Churchill, Gary A.; Lusis, Aldons J.

    2015-01-01

    Human genome-wide association studies have identified thousands of loci associated with disease phenotypes. Genome-wide association studies also have become feasible using rodent models and these have some important advantages over human studies, including controlled environment, access to tissues for molecular profiling, reproducible genotypes, and a wide array of techniques for experimental validation. Association mapping with common mouse inbred strains generally requires 100 or more strains to achieve sufficient power and mapping resolution; in contrast, sample sizes for human studies typically are one or more orders of magnitude greater than this. To enable well-powered studies in mice, we have generated high-density genotypes for ∼175 inbred strains of mice using the Mouse Diversity Array. These new data increase marker density by 1.9-fold, have reduced missing data rates, and provide more accurate identification of heterozygous regions compared with previous genotype data. We report the discovery of new loci from previously reported association mapping studies using the new genotype data. The data are freely available for download, and Web-based tools provide easy access for association mapping and viewing of the underlying intensity data for individual loci. PMID:26224782

  15. Mouse tooth development time sequence determination for the ICR/Jcl strain.

    PubMed

    Gaete, Marcia; Lobos, Nelson; Torres-Quintana, María Angélica

    2004-09-01

    To establish the normal dental development pattern of the ICR/Jcl strain of mouse, we analyzed a significant number of observations of the different developmental stages of the first mandibular molar, accurately recording the chronology of their daily embryonic development. Proliferation of the dental sheet began at day 12.5 in utero (E-12.5), the bud stage appeared at days E-13.5 and E-14.5, the cap stage was observed at days E-14.5, E-15.5 and E-16.5 and the early bell stage at day E-17.5. The presence of predentin was observed at day E-18.5 and dentin was observed 1 and 2 days after birth (D-1 and D-2). The late bell stage with presence of enamel was detected more than 3 days after birth. Embryonic and dental development in the ICR/Jcl strain of mouse is faster than in other well-known strains. The establishment of this developmental pattern will be useful for future investigations of transgenic mice. PMID:15508745

  16. Effect of mouse strain as a background for Alzheimer’s disease models on the clearance of amyloid-β

    PubMed Central

    Qosa, Hisham; Kaddoumi, Amal

    2016-01-01

    Novel animal models of Alzheimer’s disease (AD) are relentlessly being developed and existing ones are being fine-tuned; however, these models face multiple challenges associated with the complexity of the disease where most of these models do not reproduce the full phenotypical disease spectrum. Moreover, different AD models express different phenotypes that could affect their validity to recapitulate disease pathogenesis and/or response to a drug. One of the most important and understudied differences between AD models is differences in the phenotypic characteristics of the background species. Here, we used the brain clearance index (BCI) method to investigate the effect of strain differences on the clearance of amyloid β (Aβ) from the brains of four mouse strains. These mouse strains, namely C57BL/6, FVB/N, BALB/c and SJL/J, are widely used as a background for the development of AD mouse models. Findings showed that while Aβ clearance across the blood-brain barrier (BBB) was comparable between the 4 strains, levels of LRP1, an Aβ clearance protein, was significantly lower in SJL/J mice compared to other mouse strains. Furthermore, these mouse strains showed a significantly different response to rifampicin treatment with regard to Aβ clearance and effect on brain level of its clearance-related proteins. Our results provide for the first time an evidence for strain differences that could affect ability of AD mouse models to recapitulate response to a drug, and opens a new research avenue that requires further investigation to successfully develop mouse models that could simulate clinically important phenotypic characteristics of AD.

  17. Genetically diverse CC-founder mouse strains replicate the human influenza gene expression signature

    PubMed Central

    Elbahesh, Husni; Schughart, Klaus

    2016-01-01

    Influenza A viruses (IAV) are zoonotic pathogens that pose a major threat to human and animal health. Influenza virus disease severity is influenced by viral virulence factors as well as individual differences in host response. We analyzed gene expression changes in the blood of infected mice using a previously defined set of signature genes that was derived from changes in the blood transcriptome of IAV-infected human volunteers. We found that the human signature was reproduced well in the founder strains of the Collaborative Cross (CC) mice, thus demonstrating the relevance and importance of mouse experimental model systems for studying human influenza disease. PMID:27193691

  18. Genetically diverse CC-founder mouse strains replicate the human influenza gene expression signature.

    PubMed

    Elbahesh, Husni; Schughart, Klaus

    2016-01-01

    Influenza A viruses (IAV) are zoonotic pathogens that pose a major threat to human and animal health. Influenza virus disease severity is influenced by viral virulence factors as well as individual differences in host response. We analyzed gene expression changes in the blood of infected mice using a previously defined set of signature genes that was derived from changes in the blood transcriptome of IAV-infected human volunteers. We found that the human signature was reproduced well in the founder strains of the Collaborative Cross (CC) mice, thus demonstrating the relevance and importance of mouse experimental model systems for studying human influenza disease. PMID:27193691

  19. A phenotype survey of 36 mutant mouse strains with gene-targeted defects in glycosyltransferases or glycan-binding proteins

    PubMed Central

    Orr, Sally L; Le, Dzung; Long, Jeffrey M; Sobieszczuk, Peter; Ma, Bo; Tian, Hua; Fang, Xiaoqun; Paulson, James C; Marth, Jamey D; Varki, Nissi

    2013-01-01

    The consortium for functional glycomics (CFG) was a large research initiative providing networking and resources for investigators studying the role of glycans and glycan-binding proteins in health and disease. Starting in 2001, six scientific cores were established to generate data, materials and new technologies. By the end of funding in 2011, the mouse phenotype core (MPC) submitted data to a website from the phenotype screen of 36 mutant mouse strains deficient in a gene for either a glycan-binding protein (GBP) or glycosyltransferase (GT). Each mutant strain was allotted three months for analysis and screened by standard phenotype assays used in the fields of immunology, histology, hematology, coagulation, serum chemistry, metabolism and behavior. Twenty of the deficient mouse strains had been studied in other laboratories, and additional tests were performed on these strains to confirm previous observations and discover new data. The CFG constructed 16 new homozygous mutant mouse strains and completed the initial phenotype screen of the majority of these new mutant strains. In total, >300 phenotype changes were observed, but considering the over 100 assays performed on each strain, most of the phenotypes were unchanged. Phenotype differences include abnormal testis morphology in GlcNAcT9- and Siglec-H-deficient mice and lethality in Pomgnt1-deficient mice. The numerous altered phenotypes discovered, along with the consideration of the significant findings of normality, will provide a platform for future characterization to understand the important roles of glycans and GBPs in the mechanisms of health and disease. PMID:23118208

  20. Strain-dependent Damage in Mouse Lung After Carbon Ion Irradiation

    SciTech Connect

    Moritake, Takashi; Fujita, Hidetoshi; Yanagisawa, Mitsuru; Nakawatari, Miyako; Imadome, Kaori; Nakamura, Etsuko; Iwakawa, Mayumi; Imai, Takashi

    2012-09-01

    Purpose: To examine whether inherent factors produce differences in lung morbidity in response to carbon ion (C-ion) irradiation, and to identify the molecules that have a key role in strain-dependent adverse effects in the lung. Methods and Materials: Three strains of female mice (C3H/He Slc, C57BL/6J Jms Slc, and A/J Jms Slc) were locally irradiated in the thorax with either C-ion beams (290 MeV/n, in 6 cm spread-out Bragg peak) or with {sup 137}Cs {gamma}-rays as a reference beam. We performed survival assays and histologic examination of the lung with hematoxylin-eosin and Masson's trichrome staining. In addition, we performed immunohistochemical staining for hyaluronic acid (HA), CD44, and Mac3 and assayed for gene expression. Results: The survival data in mice showed a between-strain variance after C-ion irradiation with 10 Gy. The median survival time of C3H/He was significantly shortened after C-ion irradiation at the higher dose of 12.5 Gy. Histologic examination revealed early-phase hemorrhagic pneumonitis in C3H/He and late-phase focal fibrotic lesions in C57BL/6J after C-ion irradiation with 10 Gy. Pleural effusion was apparent in C57BL/6J and A/J mice, 168 days after C-ion irradiation with 10 Gy. Microarray analysis of irradiated lung tissue in the three mouse strains identified differential expression changes in growth differentiation factor 15 (Gdf15), which regulates macrophage function, and hyaluronan synthase 1 (Has1), which plays a role in HA metabolism. Immunohistochemistry showed that the number of CD44-positive cells, a surrogate marker for HA accumulation, and Mac3-positive cells, a marker for macrophage infiltration in irradiated lung, varied significantly among the three mouse strains during the early phase. Conclusions: This study demonstrated a strain-dependent differential response in mice to C-ion thoracic irradiation. Our findings identified candidate molecules that could be implicated in the between-strain variance to early

  1. Deficiency in DNA repair in mouse lymphoma strain L5178Y-S.

    PubMed Central

    Evans, H H; Ricanati, M; Horng, M F

    1987-01-01

    The production and repair of radiation-induced DNA damage were measured by filter elution in strains of mouse lymphoma L5178Y cells differing in their sensitivity to ionizing radiation. The induction of radiation-induced damage, as measured by filter elution at pH 12.1, 9.6, and 7.2, was similar in the resistant strain LY-R and the sensitive strain LY-S. The repair of single-strand breaks and alkali-labile sites, as measured by filter elution at pH 12.1 at various times after irradiation, was somewhat slower in strain LY-S than in strain LY-R, although after a 20-min repair period the extent of repair was equal in the two strains. However, when filter elution was performed at either pH 9.6 or pH 7.2, the repair of x-radiation-induced damage was much less extensive in strain LY-S than in strain LY-R. We have assumed that the extent of filter elution at pH 9.6 is a measure of the occurrence of frank double-strand breaks as well as closely opposing single-strand breaks and pH 9.6-labile sites (and combinations thereof), and that the extent of elution at pH 7.2 is a measure of the occurrence of frank double-strand breaks alone. If these assumptions are correct, the results suggest that the sensitivity of strain LY-S to the cytotoxic effects of ionizing radiation is caused by a deficiency in the ability of this strain to repair frank double-strand breaks and pH 9.6-labile lesions. The repair of pH 9.6-labile lesions was temperature sensitive in strain LY-S, as previously found for cellular recovery processes in this strain. Two independent radiation-resistant variants of strain LY-S, isolated after protracted exposure of LY-S cells to low-dose-rate radiation, showed a deficiency in the repair of pH 9.6-labile lesions similar to that observed in strain LY-S. However, the repair of frank double-strand breaks was more extensive in the radiation-resistant variants than in strain LY-S and was similar in extent to that occurring in strain LY-R after a 60-min postirradiation

  2. Optimization of protocols for derivation of mouse embryonic stem cell lines from refractory strains, including the non obese diabetic mouse.

    PubMed

    Davies, Timothy J; Fairchild, Paul J

    2012-07-01

    The derivation of pluripotent embryonic stem cells (ESCs) from a variety of genetic backgrounds remains a desirable objective in the generation of mice functionally deficient in genes of interest and the modeling of human disease. Nevertheless, disparity in the ease with which different strains of mice yield ESC lines has long been acknowledged. Indeed, the generation of bona fide ESCs from the non obese diabetic (NOD) mouse, a well-characterized model of human type I diabetes, has historically proved especially difficult to achieve. Here, we report the development of protocols for the derivation of novel ESC lines from C57Bl/6 mice based on the combined use of high concentrations of leukemia inhibitory factor and serum-replacement, which is equally applicable to fresh and cryo-preserved embryos. Further, we demonstrate the success of this approach using Balb/K and CBA/Ca mice, widely considered to be refractory strains. CBA/Ca ESCs contributed to the somatic germ layers of chimeras and displayed a very high competence at germline transmission. Importantly, we were able to use the same protocol for the derivation of ESC lines from nonpermissive NOD mice. These ESCs displayed a normal karyotype that was robustly stable during long-term culture, were capable of forming teratomas in vivo and germline competent chimeras after injection into recipient blastocysts. Further, these novel ESC lines efficiently formed embryoid bodies in vitro and could be directed in their differentiation along the dendritic cell lineage, thus illustrating their potential application to the generation of cell types of relevance to the pathogenesis of type I diabetes. PMID:21933027

  3. Ultrastructural and Associated Studies on Experimental Mastitis in the Mouse Produced by Three Strains of Streptococcus

    PubMed Central

    Chandler, R. L.

    1973-01-01

    Ultrastructural studies were made on mastitis produced experimentally in the mouse by 3 different strains of streptococcus. The first strain of Str. agalactiae produced cellular changes detectable by electron microscopy as early as 6 hours after inoculation and at 48 hours alterations to secretory epithelium, lumenal contents and subepithelial tissue were very evident; later samplings showed more advanced changes. Cocci were seen in the lumens and within secretory cells; at later stages they showed degenerative changes themselves. A second strain of Str. agalactiae produced similar general changes; milk protein masses were common in the lumens, and rod-shaped crystals were observed. Cocci were seen free in the lumens, in lumenal macrophages, within secretory cells and, in later stages, in the subepithelial tissue. The possibility of their penetrating the epithelium either through the epithelial cell substance or through the intercellular space is discussed. Studies with a strain of Str. uberis indicated a lower level of pathogenicity but electron microscopy showed a variety of cellular changes. It was clear from comparative studies, including the use of heat-killed cocci, that very large numbers of bacteria must be present in a given specimen for their identification in ultrathin sections of mammary gland. ImagesFigs. 5-8Figs. 1-4 PMID:4736957

  4. Identification of 17 hearing impaired mouse strains in the TMGC ENU-mutagenesis screen

    SciTech Connect

    Kermany, Mohammad; Parker, Lisan; Guo, Yun-Kai; Miller, Darla R; Swanson, Douglas J; Yoo, Tai-June; Goldowitz, Daniel; Zuo, Jian

    2006-01-01

    The Tennessee Mouse Genome Consortium (TMGC) employed an N-ethyl-N-nitrosourea (ENU)-mutagenesis scheme to identify mouse recessive mutants with hearing phenotypes. We employed auditory brainstem responses (ABR) to click and 8, 16, and 32 kHz stimuli and screened 285 pedigrees (1819 mice of 8-11 weeks old in various mixed genetic backgrounds) each bred to carry a homozygous ENU-induced mutation. To define mutant pedigrees, we measured P12 mice per pedigree in P2 generations and used a criterion where the mean ABR threshold per pedigree was two standard deviations above the mean of all offspring from the same parental strain. We thus identified 17 mutant pedigrees (6%), all exhibiting hearing loss at high frequencies (P16 kHz) with an average threshold elevation of 30-35 dB SPL. Interestingly, four mutants showed sex-biased hearing loss and six mutants displayed wide range frequency hearing loss. Temporal bone histology revealed that six of the first nine mutants displayed cochlear morphological defects: degeneration of spiral ganglia, spiral ligament fibrocytes or inner hair cells (but not outer hair cells) mostly in basal turns. In contrast to other ENU-mutagenesis auditory screens, our screen identified high-frequency, mild and sex-biased hearing defects. Further characterization of these 17 mouse models will advance our understanding of presbycusis and noise-induced hearing loss in humans.

  5. Proliferation Potential of Müller Glia after Retinal Damage Varies between Mouse Strains

    PubMed Central

    Suga, Akiko; Sadamoto, Kazuyo; Fujii, Momo; Mandai, Michiko; Takahashi, Masayo

    2014-01-01

    Retinal Müller glia can serve as a source for regeneration of damaged retinal neurons in fish, birds and mammals. However, the proliferation rate of Müller glia has been reported to be low in the mammalian retina. To overcome this problem, growth factors and morphogens have been studied as potent promoters of Müller glial proliferation, but the molecular mechanisms that limit the proliferation of Müller glia in the mammalian retina remain unknown. In the present study, we found that the degree of damage-induced Müller glia proliferation varies across mouse strains. In mouse line 129×1/SvJ (129), there was a significantly larger proliferative response compared with that observed in C57BL/6 (B6) after photoreceptor cell death. Treatment with a Glycogen synthase kinase 3 (GSK3) inhibitor enhanced the proliferation of Müller glia in 129 but not in B6 mouse retinas. We therefore focused on the different gene expression patterns during retinal degeneration between B6 and 129. Expression levels of Cyclin D1 and Nestin correlated with the degree of Müller glial proliferation. A comparison of genome-wide gene expression between B6 and 129 showed that distinct sets of genes were upregulated in the retinas after damage, including immune response genes and chromatin remodeling factors. PMID:24747725

  6. Reward-Related Behavioral Paradigms for Addiction Research in the Mouse: Performance of Common Inbred Strains

    PubMed Central

    Feyder, Michael; Brigman, Jonathan L.; Crombag, Hans S.; Saksida, Lisa M.; Bussey, Timothy J.; Holmes, Andrew

    2011-01-01

    The mouse has emerged as a uniquely valuable species for studying the molecular and genetic basis of complex behaviors and modeling neuropsychiatric disease states. While valid and reliable preclinical assays for reward-related behaviors are critical to understanding addiction-related processes, and various behavioral procedures have been developed and characterized in rats and primates, there have been relatively few studies using operant-based addiction-relevant behavioral paradigms in the mouse. Here we describe the performance of the C57BL/6J inbred mouse strain on three major reward-related paradigms, and replicate the same procedures in two other commonly used inbred strains (DBA/2J, BALB/cJ). We examined Pavlovian-instrumental transfer (PIT) by measuring the ability of an auditory cue associated with food reward to promote an instrumental (lever press) response. In a separate experiment, we assessed the acquisition and extinction of a simple stimulus-reward instrumental behavior on a touchscreen-based task. Reinstatement of this behavior was then examined following either continuous exposure to cues (conditioned reinforcers, CRs) associated with reward, brief reward and CR exposure, or brief reward exposure followed by continuous CR exposure. The third paradigm examined sensitivity of an instrumental (lever press) response to devaluation of food reward (a probe for outcome insensitive, habitual behavior) by repeated pairing with malaise. Results showed that C57BL/6J mice displayed robust PIT, as well as clear extinction and reinstatement, but were insensitive to reinforcer devaluation. DBA/2J mice showed good PIT and (rewarded) reinstatement, but were slow to extinguish and did not show reinforcer devaluation or significant CR-reinstatement. BALB/cJ mice also displayed good PIT, extinction and reinstatement, and retained instrumental responding following devaluation, but, unlike the other strains, demonstrated reduced Pavlovian approach behavior (food

  7. Experimenter effects on behavioral test scores of eight inbred mouse strains under the influence of ethanol

    PubMed Central

    Bohlen, Martin; Hayes, Erika R.; Bohlen, Benjamin; Bailoo, Jeremy; Crabbe, John C.; Wahlsten, Douglas

    2016-01-01

    Eight standard inbred mouse strains were evaluated for ethanol effects on a refined battery of behavioral tests in a study that was originally designed to assess the influence of rat odors in the colony on mouse behaviors. As part of the design of the study, two experimenters conducted the tests, and the study was carefully balanced so that equal numbers of mice in all groups and times of day were tested by each experimenter. A defect in airflow in the facility compromised the odor manipulation, and in fact the different odor exposure groups did not differ in their behaviors. The two experimenters, however, obtained markedly different results for three of the tests. Certain of the experimenter effects arose from the way they judged behaviors that were not automated and had to be rated by the experimenter, such as slips on the balance beam. Others were not evident prior to ethanol injection but had a major influence after the injection. For several measures, the experimenter effects were notably different for different inbred strains. Methods to evaluate and reduce the impact of experimenter effects in future research are discussed. PMID:24933191

  8. Acquisition of nonspecific Bartonella strains by the northern grasshopper mouse (Onychomys leucogaster)

    USGS Publications Warehouse

    Bai, Y.; Kosoy, M.Y.; Cully, J.F.; Bala, T.; Ray, C.; Collinge, S.K.

    2007-01-01

    Rodent-associated Bartonella species are generally host-specific parasites in North America. Here evidence that Bartonella species can 'jump' between host species is presented. Northern grasshopper mice and other rodents were trapped in the western USA. A study of Bartonella infection in grasshopper mice demonstrated a high prevalence that varied from 25% to 90% by location. Bartonella infection was detected in other rodent species with a high prevalence as well. Sequence analyses of gltA identified 29 Bartonella variants in rodents, 10 of which were obtained from grasshopper mice. Among these 10, only six variants were specific to grasshopper mice, whereas four were identical to variants specific to deer mice or 13-lined ground squirrels. Fourteen of 90 sequenced isolates obtained from grasshopper mice were strains found more commonly in other rodent species and were apparently acquired from these animals. The ecological behavior of grasshopper mice may explain the occurrence of Bartonella strains in occasional hosts. The observed rate at which Bartonella jumps from a donor host species to the grasshopper mouse was directly proportional to a metric of donor host density and to the prevalence of Bartonella in the donor host, and inversely proportional to the same parameters for the grasshopper mouse. ?? 2007 Federation of European Microbiological Societies.

  9. Intrinsic differences in BRITE adipogenesis of primary adipocytes from two different mouse strains.

    PubMed

    Li, Yongguo; Bolze, Florian; Fromme, Tobias; Klingenspor, Martin

    2014-09-01

    BRITE (brown-in-white) cells are brown adipocyte-like cells found in white adipose tissue (WAT) of rodents and/or humans. The recruitment of BRITE adipocytes, referred to as the browning of WAT, is hallmarked by the expression of UCP1 and exerts beneficial metabolic effects. Here we address whether beyond systemic cues depot- and strain-specific variation in BRITE recruitment is determined by a cellular program intrinsic to progenitors. Therefore we compared the browning capacity of serum and investigated brown and BRITE adipogenesis in primary cultures of stromal-vascular cells isolated from interscapular brown adipose tissue (iBAT), inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) in two inbred mouse strains C57BL/6J (B6, a strain with low browning propensity) and 129/S6SvEv (129, a strain with high browning propensity). Paradoxically, serum collected from B6 mice was more potent in the promotion of browning than serum collected from 129 mice. Nevertheless, we demonstrate that depot- and strain-specific differences observed in vivo are pheno-copied in primary cultures in vitro, as judged by UCP1 expression and by functional analysis. Notably, primary adipocytes from 129 mice had a higher capacity for isoproterenol-induced uncoupled respiration than B6. We conclude that cues intrinsic to the progenitor cells contribute to differential BRITE adipogenesis. Further analyses demonstrate that these cues are independent of autocrine/paracrine mechanisms, BRITE progenitor abundance and genetic variation in the gene regulatory region of Ucp1 but rather depend on trans-acting factors. These results provide new insights on the molecular basis of strain and depot-specific differences in BRITE adipogenesis. PMID:24953778

  10. Generation of live offspring from vitrified mouse oocytes of C57BL/6J strain.

    PubMed

    Kohaya, Natsuki; Fujiwara, Katsuyoshi; Ito, Junya; Kashiwazaki, Naomi

    2013-01-01

    In mammals, unfertilized oocytes are one of the most available stages for cryopreservation because the cryopreserved oocytes can be used for assisted reproductive technologies, including in vitro fertilization (IVF) and intracytoplasmic sperm injection. However, it has generally been reported that the fertility and developmental ability of the oocytes are reduced by cryopreservation. C57BL/6J mice, an inbred strain, are used extensively for the production of transgenic and knockout mice. If the oocytes from C57BL/6J mice can be successfully cryopreserved, the cryopreservation protocol used will contribute to the high-speed production of not only gene-modified mice but also hybrid mice. Very recently, we succeeded in the vitrification of mouse oocytes derived from ICR (outbred) mice. However, our protocol can be applied to the vitrification of oocytes from an inbred strain. The aim of the present study was to establish the vitrification of oocytes from C57BL/6J mice. First, the effect of cumulus cells on the ability of C57BL/6J mouse oocytes to fertilize and develop in vitro was examined. The fertility and developmental ability of oocyte-removed cumulus cells (i.e., denuded oocytes, or DOs) after IVF were reduced compared to cumulus oocyte complexes (COCs) in both fresh and cryopreserved groups. Vitrified COCs showed significantly (P<0.05) higher fertility and ability to develop into the 2-cell and blastocyst stages compared to the vitrified DOs with cumulus cells and vitrified DOs alone. The vitrified COCs developed to term at a high success rate, equivalent to the rate obtained with IVF using fresh COCs. Taken together, our results demonstrate that we succeeded for the first time in the vitrification of mouse oocytes from C57BL/6J mice. Our findings will also contribute to the improvement of oocyte vitrification not only in animals but also in clinical applications for human infertility. PMID:23516430

  11. Multifaceted strain-specific effects in a mouse model of depression and of antidepressant reversal.

    PubMed

    Ibarguen-Vargas, Yadira; Surget, Alexandre; Touma, Chadi; Palme, Rupert; Belzung, Catherine

    2008-11-01

    Etiopathogenesis of depression and the cause of insensitivity to treatment remain poorly understood, although genetic makeup has been established as a contributing factor. The isogenicity of inbred mouse strains provides a useful tool for investigating the link between genes and behavior or drug response. Hence, our aim was to identify inbred mouse strains (among A/J, BALB/c, C3H, C57BL/6, CBA, DBA and FVB) sensitive to a 9-week period of unpredictable chronic mild stress (UCMS) and, from the fifth week onward, to the reversal effect of an antidepressant (AD) (imipramine, 20mg/kg/day i.p.) on various depression-related changes: physical, behavioral and neuroendocrine states. UCMS induced a significant deterioration of the coat state (in all the strains), blunted emotional reactivity in the novelty-suppressed feeding (NSF) test (A/J, BALB/c, C57BL/6), and changes in the level of fecal corticosterone metabolites (BALB/c, C57BL/6, DBA, FVB). Imipramine treatment reversed the UCMS-induced alterations of the coat state (BALB/c, DBA), in the NSF test (A/J, BALB/c, C57BL/6) and in fecal corticosterone metabolites (BALB/c, C57BL/6). C3H, CBA and FVB mice were irresponsive to imipramine treatment. It is noteworthy that UCMS-induced physical or behavioral changes occurred without hypothalamo-pituitary-adrenal (HPA) axis alterations in some strains (A/J, C3H, CBA), although the AD-induced reversal of these changes in BALB/c and C57BL/6 was associated with HPA axis normalization. Finally, UCMS is shown to discriminate various alterations and to replicate in a strain-dependent manner diverse profiles reminiscent of human disease subtypes. UCMS may thus enable the selection of strains suitable for investigating specific depression-related features and could be an appropriate model for identifying genetic factors associated with increased vulnerability, specific symptoms of affective disorders, and AD resistance. PMID:18790573

  12. Genome sequences of a mouse-avirulent and a mouse-virulent strain of Ross River virus.

    PubMed

    Faragher, S G; Meek, A D; Rice, C M; Dalgarno, L

    1988-04-01

    The nucleotide sequence of the genomic RNA of a mouse-avirulent strain of Ross River virus, RRV NB5092 (isolated in 1969), has been determined and the corresponding sequence for the prototype mouse-virulent strain, RRV T48 (isolated in 1959), has been completed. The RRV NB5092 genome is approximately 11,674 nucleotides in length, compared with 11,853 nucleotides for RRV T48. RRV NB5092 and RRV T48 have the same genome organization. For both viruses an untranslated region of 80 nucleotides at the 5' end of the genome is followed by a 7440-nucleotide open reading frame which is interrupted after 5586 nucleotides by a single opal termination codon. By homology with other alphaviruses, the 5586-nucleotide open reading frame encodes the nonstructural proteins nsP1, nsP2, and nsP3; a fourth nonstructural protein, nsP4, is produced by read-through of the opal codon. The RRV nonstructural proteins show strong homology with the corresponding proteins of Sindbis virus and Semliki Forest virus in terms of size, net charge, and hydropathy characteristics. However, homology is not uniform between or within the proteins; nsP1, nsP2, and nsP4 contain extended domains which are highly conserved between alphaviruses, while the C-terminal region of nsP3 shows little conservation in sequence or length between alphaviruses. An untranslated "junction" region of 44 nucleotides (for RRV NB5092) or 47 nucleotides (for RRV T48) separates the nonstructural and structural protein coding regions. The structural proteins (capsid-E3-E2-6K-E1) are translated from an open reading frame of 3762 nucleotides which is followed by a 3'-untranslated region of approximately 348 nucleotides (for RRV NB5092) or 524 nucleotides (for RRV T48). Excluding deletions and insertions, the genomes of RRV NB5092 and RRV T48 differ at 284 nucleotides, representing a sequence divergence of 2.38%. Sequence deletions or insertions were found only in the noncoding regions and include a 173-nucleotide deletion in the 3

  13. Compressive viscoelasticity of freshly excised mouse skin is dependent on specimen thickness, strain level and rate.

    PubMed

    Wang, Yuxiang; Marshall, Kara L; Baba, Yoshichika; Lumpkin, Ellen A; Gerling, Gregory J

    2015-01-01

    Although the skin's mechanical properties are well characterized in tension, little work has been done in compression. Here, the viscoelastic properties of a population of mouse skin specimens (139 samples from 36 mice, aged 5 to 34 weeks) were characterized upon varying specimen thickness, as well as strain level and rate. Over the population, we observed the skin's viscoelasticity to be quite variable, yet found systematic correlation of residual stress ratio with skin thickness and strain, and of relaxation time constants with strain rates. In particular, as specimen thickness ranged from 211 to 671 μm, we observed significant variation in both quasi-linear viscoelasticity (QLV) parameters, the relaxation time constant (τ1 = 0.19 ± 0.10 s) and steady-state residual stress ratio (G∞ = 0.28 ± 0.13). Moreover, when τ1 was decoupled and fixed, we observed that G∞ positively correlated with skin thickness. Second, as steady-state stretch was increased (λ∞ from 0.22 to 0.81), we observed significant variation in both QLV parameters (τ1 = 0.26 ± 0.14 s, G∞ = 0.47 ± 0.17), and when τ1 was fixed, G∞ positively correlated with stretch level. Third, as strain rate was increased from 0.06 to 22.88 s-1, the median time constant τ1 varied from 1.90 to 0.31 s, and thereby negatively correlated with strain rate. These findings indicate that the natural range of specimen thickness, as well as experimental controls of compression level and rate, significantly influence measurements of skin viscoelasticity. PMID:25803703

  14. Compressive Viscoelasticity of Freshly Excised Mouse Skin Is Dependent on Specimen Thickness, Strain Level and Rate

    PubMed Central

    Wang, Yuxiang; Marshall, Kara L.; Baba, Yoshichika; Lumpkin, Ellen A.; Gerling, Gregory J.

    2015-01-01

    Although the skin’s mechanical properties are well characterized in tension, little work has been done in compression. Here, the viscoelastic properties of a population of mouse skin specimens (139 samples from 36 mice, aged 5 to 34 weeks) were characterized upon varying specimen thickness, as well as strain level and rate. Over the population, we observed the skin’s viscoelasticity to be quite variable, yet found systematic correlation of residual stress ratio with skin thickness and strain, and of relaxation time constants with strain rates. In particular, as specimen thickness ranged from 211 to 671 μm, we observed significant variation in both quasi-linear viscoelasticity (QLV) parameters, the relaxation time constant (τ1 = 0.19 ± 0.10 s) and steady-state residual stress ratio (G∞ = 0.28 ± 0.13). Moreover, when τ1 was decoupled and fixed, we observed that G∞ positively correlated with skin thickness. Second, as steady-state stretch was increased (λ∞ from 0.22 to 0.81), we observed significant variation in both QLV parameters (τ1 = 0.26 ± 0.14 s, G∞ = 0.47 ± 0.17), and when τ1 was fixed, G∞ positively correlated with stretch level. Third, as strain rate was increased from 0.06 to 22.88 s−1, the median time constant τ1 varied from 1.90 to 0.31 s, and thereby negatively correlated with strain rate. These findings indicate that the natural range of specimen thickness, as well as experimental controls of compression level and rate, significantly influence measurements of skin viscoelasticity. PMID:25803703

  15. Gliopathy of Demyelinating and Non-Demyelinating Strains of Mouse Hepatitis Virus

    PubMed Central

    Kenyon, Lawrence C.; Biswas, Kaushiki; Shindler, Kenneth S.; Nabar, Manasi; Stout, Marjorie; Hingley, Susan T.; Grinspan, Judith B.; Das Sarma, Jayasri

    2015-01-01

    Demyelination in the central nervous system induced by neurovirulent strains of Mouse Hepatitis Virus (MHV) is mediated by the viral spike glycoprotein, but it is not clear whether the mechanism of this disease pathology involves direct viral infection of oligodendrocytes. Detailed studies of glial cell tropism of MHV are presented, demonstrating that direct MHV infection of oligodendrocytes differs between demyelinating (RSA59) and non-demyelinating (RSMHV2) viral strains both in vitro and in vivo. Our results indicate that direct injury of mature oligodendrocytes is an important mechanism of virus-induced demyelination. In vivo, RSA59 infection was identified in spinal cord gray and white matter, but infected oligodendrocytes were restricted to white matter. In contrast, RSMHV2 infection was restricted to gray matter neurons and was not localized to oligodendrocytes. In vitro, RSA59 can infect both oligodendrocyte precursors and differentiated oligodendrocytes, whereas RSMHV2 can infect oligodendrocyte precursors but not differentiated oligodendrocytes. Viral spreading through axonal means to white matter and release of the demyelinating strain MHV at the nerve end is critical for oligodendrocytes infection and subsequent demyelination. Understanding the mechanisms by which known viruses effect demyelination in this animal model has important therapeutic implications in the treatment of human demyelinating disease. PMID:26733813

  16. Differing rates of cholesterol absorption among inbred mouse strains yield differing levels of HDL-cholesterol.

    PubMed

    Sontag, Timothy J; Chellan, Bijoy; Getz, Godfrey S; Reardon, Catherine A

    2013-09-01

    Inbred strains of mice with differing susceptibilities to atherosclerosis possess widely varying plasma HDL levels. Cholesterol absorption and lipoprotein formation were compared between atherosclerosis-susceptible, low-HDL C57BL6/J mice and atherosclerosis-resistant, high-HDL FVBN/J mice. [(3)H]cholesterol and triglyceride appeared in the plasma of FVB mice gavaged with cholesterol in olive oil at a much higher rate than in C57 mice. The plasma cholesterol was found almost entirely as HDL-cholesterol in both strains. Inhibition of lipoprotein catabolism with Tyloxapol revealed that the difference in the rate of [(3)H]cholesterol appearance in the plasma was due entirely to a greater rate of chylomicron secretion from the intestine of the FVB mice. Lipid absorption into the 2nd quarter of the small intestine is greater in the FVB mice and indicates that this region may contain the factors that give rise to the differences in absorption observed between the two mouse strains. Additionally, ad libitum feeding prior to cholesterol gavage accentuates the absorption rate differences compared with fasting. The resultant remodeling of the increased levels of chylomicron in the plasma may contribute to increased plasma HDL. Intestinal gene expression analysis reveals several genes that may play a role in these differences, including microsomal triglyceride transfer protein and ABCG8. PMID:23812556

  17. Phenotypic Characterization of the KK/HlJ Inbred Mouse Strain

    PubMed Central

    Berndt, A.; Sundberg, B. A.; Silva, K. A.; Kennedy, V. E.; Richardson, M. A.; Li, Q.; Bronson, R. T.; Uitto, J.; Sundberg, J. P.

    2014-01-01

    Detailed histopathological diagnoses of inbred mouse strains are important for interpreting research results and defining novel models of human diseases. The aim of this study was to histologically detect lesions affecting the KK/HlJ inbred strain. Mice were examined at 6, 12, and 20 months of age and near natural death (ie, moribund mice). Histopathological lesions were quantified by percentage of affected mice per age group and sex. Predominant lesions were mineralization, hyperplasia, and fibro-osseous lesions. Mineralization was most frequently found in the connective tissue dermal sheath of vibrissae, the heart, and the lung. Mineralization was also found in many other organs but to a lesser degree. Hyperplasia was found most commonly in the pancreatic islets, and fibro-osseous lesions were observed in several bones. The percentage of lesions increased with age until 20 months. This study shows that KK/HlJ mice demonstrate systemic aberrant mineralization, with greatest frequency in aged mice. The detailed information about histopathological lesions in the inbred strain KK/HlJ can help investigators to choose the right model and correctly interpret the experimental results. PMID:24009271

  18. Polymorphisms in the taste receptor gene (Tas1r3) region are associated with saccharin preference in 30 mouse strains.

    PubMed

    Reed, D R; Li, S; Li, X; Huang, L; Tordoff, M G; Starling-Roney, R; Taniguchi, K; West, D B; Ohmen, J D; Beauchamp, G K; Bachmanov, A A

    2004-01-28

    The results of recent studies suggest that the mouse Sac (saccharin preference) locus is identical to the Tas1r3 (taste receptor) gene. The goal of this study was to identify Tas1r3 sequence variants associated with saccharin preference in a large number of inbred mouse strains. Initially, we sequenced approximately 6.7 kb of the Tas1r3 gene and its flanking regions from six inbred mouse strains with high and low saccharin preference, including the strains in which the Sac alleles were described originally (C57BL/6J, Sac(b); DBA/2J, Sac(d)). Of the 89 sequence variants detected among these six strains, eight polymorphic sites were significantly associated with preferences for 1.6 mm saccharin. Next, each of these eight variant sites were genotyped in 24 additional mouse strains. Analysis of the genotype-phenotype associations in all 30 strains showed the strongest association with saccharin preference at three sites: nucleotide (nt) -791 (3 bp insertion/deletion), nt +135 (Ser45Ser), and nt +179 (Ile60Thr). We measured Tas1r3 gene expression, transcript size, and T1R3 immunoreactivity in the taste tissue of two inbred mouse strains with different Tas1r3 haplotypes and saccharin preferences. The results of these experiments suggest that the polymorphisms associated with saccharin preference do not act by blocking gene expression, changing alternative splicing, or interfering with protein translation in taste tissue. The amino acid substitution (Ile60Thr) may influence the ability of the protein to form dimers or bind sweeteners. Here, we present data for future studies directed to experimentally confirm the function of these polymorphisms and highlight some of the difficulties of identifying specific DNA sequence variants that underlie quantitative trait loci. PMID:14749438

  19. Using digital image correlation to determine bone surface strains during loading and after adaptation of the mouse tibia.

    PubMed

    Sztefek, Pavel; Vanleene, Maximilien; Olsson, Robin; Collinson, Rebecca; Pitsillides, Andrew A; Shefelbine, Sandra

    2010-03-01

    Previous models of cortical bone adaptation, in which loading is imposed on the bone, have estimated the strains in the tissue using strain gauges, analytical beam theory, or finite element analysis. We used digital image correlation (DIC), tracing a speckle pattern on the surface of the bone during loading, to determine surface strains in a murine tibia during compressive loading through the knee joint. We examined whether these surface strains in the mouse tibia are modified following two weeks of load-induced adaptation by comparison with contralateral controls. Results indicated non-uniform strain patterns with isolated areas of high strain (0.5%), particularly on the medial side. Strain measurements were reproducible (standard deviation of the error 0.03%), similar between specimens, and in agreement with strain gauge measurements (between 0.1 and 0.2% strain). After structural adaptation, strains were more uniform across the tibial surface, particularly on the medial side where peak strains were reduced from 0.5% to 0.3%. Because DIC determines local strains over the entire surface, it will provide a better understanding of how strain stimulus influences the bone response during adaptation. PMID:20005517

  20. An enriched environment improves cognitive performance in mice from the senescence-accelerated prone mouse 8 strain

    PubMed Central

    Yuan, Zhenyun; Wang, Mingwei; Yan, Baoyong; Gu, Ping; Jiang, Xiangming; Yang, Xiufen; Cui, Dongsheng

    2012-01-01

    In this study, we examined 3-month-old female mice from the senescence-accelerated prone mouse 8 strain and age-matched homologous normal aging female mice from the senescence accelerated- resistant mouse 1 strain. Mice from each strain were housed in an enriched environment (including a platform, running wheels, tunnel, and some toys) or a standard environment for 3 months. The mice housed in the enriched environment exhibited shorter escape latencies and a greater percentage of time in the target quadrant in the Morris water maze test, and they exhibited reduced errors and longer latencies in step-down avoidance experiments compared with mice housed in the standard environment. Correspondently, brain-derived neurotrophic factor mRNA and protein expression in the hippocampus was significantly higher in mice housed in the enriched environment compared with those housed in the standard environment, and the level of hippocampal brain-derived neurotrophic factor protein was positively correlated with the learning and memory abilities of mice from the senescence-accelerated prone mouse 8 strain. These results suggest that an enriched environment improved cognitive performance in mice form the senescence-accelerated prone mouse 8 strain by increasing brain-derived neurotrophic factor expression in the hippocampus. PMID:25624804

  1. Attention to Background Strain Is Essential for Metabolic Research: C57BL/6 and the International Knockout Mouse Consortium.

    PubMed

    Fontaine, Danielle A; Davis, Dawn Belt

    2016-01-01

    The International Knockout Mouse Consortium (IKMC) introduces its targeted constructs into C57BL/6N embryonic stem cells. However, breeding with a Cre-recombinase and/or Flp-recombinase mouse is required for the generation of a null allele with the IKMC cassette. Many recombinase strains are in the C57BL/6J background, resulting in knockout animals on a mixed strain background. This can lead to variability in metabolic data and the use of improper control groups. While C57BL/6N and C57BL/6J are derived from the same parental C57BL/6 strain, there are key genotypic and phenotypic differences between these substrains. Many researchers may not even be aware of these differences, as the shorthand C57BL/6 is often used to describe both substrains. We found that 58% of articles involving genetically modified mouse models did not completely address background strain. This review will describe these two substrains and highlight the importance of separate consideration in mouse model development. Our aim is to increase awareness of this issue in the diabetes research community and to provide practical strategies to enable researchers to avoid mixed strain animals when using IKMC knockout mice. PMID:26696638

  2. A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains

    PubMed Central

    2013-01-01

    Background The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. Results We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. Conclusions Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains. PMID:23902802

  3. Tumor blood flow differs between mouse strains: consequences for vasoresponse to photodynamic therapy.

    PubMed

    Mesquita, Rickson C; Han, Sung Wan; Miller, Joann; Schenkel, Steven S; Pole, Andrew; Esipova, Tatiana V; Vinogradov, Sergei A; Putt, Mary E; Yodh, Arjun G; Busch, Theresa M

    2012-01-01

    Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies. PMID:22624014

  4. Tumor Blood Flow Differs between Mouse Strains: Consequences for Vasoresponse to Photodynamic Therapy

    PubMed Central

    Mesquita, Rickson C.; Han, Sung Wan; Miller, Joann; Schenkel, Steven S.; Pole, Andrew; Esipova, Tatiana V.; Vinogradov, Sergei A.; Putt, Mary E.; Yodh, Arjun G.; Busch, Theresa M.

    2012-01-01

    Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies. PMID:22624014

  5. Effects of Diet and Strain on Mouse Serum and Tissue Retinoid Concentrations

    PubMed Central

    Obrochta, Kristin M.; Kane, Maureen A.; Napoli, Joseph L.

    2014-01-01

    The relationship between dietary vitamin A and all-trans-retinoic acid levels in serum and tissues had not been quantified. We determined the impact of dietary vitamin A on retinoid levels in serum, liver, kidney, testis, and epididymal white adipose of five mouse strains: AKR/J; BALB/cByJ; C3H/HeJ; C57BL/6J; 129S1/SvImJ. Retinoids were quantified in mice fed copious vitamin A (lab chow, ≥20 IU/g) followed by one month feeding a vitamin A-sufficient diet (4 IU/g), or after three generations of feeding a vitamin A-sufficient diet. Retinol and retinyl esters were measured by high-performance liquid chromatography with ultraviolet absorbance detection. All-trans-retinoic acid was quantified by liquid chromatography tandem mass spectrometry. The amounts of dietary vitamin A had long-term strain-specific effects on tissue retinyl ester, retinol and all-trans-retinoic acid concentrations. Three generations of feeding a vitamin A-sufficient diet decreased all-trans-retinoic acid in most tissues of most strains, in some cases more than 60%, compared to a diet with copious vitamin A. With both diets, all-trans-retinoic acid concentrations maintained an order of liver ≈ testis > kidney > white adipose tissue ≈ serum. Neither retinol nor all-trans-retinoic acid in serum reflected all-trans-retinoic acid concentrations in tissues. Strain and tissue-specific differences in retinol and all-trans-retinoic acid altered by different amounts of dietary vitamin A could have profound effects on retinoid action. This would be the case especially with the increased all-trans-retinoic acid values associated with the amounts of vitamin A and its precursors (carotenoids) in chow diets. PMID:24911926

  6. Marine Mammal Brucella Reference Strains Are Attenuated in a BALB/c Mouse Model.

    PubMed

    Nymo, Ingebjørg H; Arias, Maykel A; Pardo, Julián; Álvarez, María Pilar; Alcaraz, Ana; Godfroid, Jacques; Jiménez de Bagüés, María Pilar

    2016-01-01

    Brucellosis is a zoonosis of worldwide distribution with numerous animal host species. Since the novel isolation of Brucella spp. from marine mammals in 1994 the bacteria have been isolated from various marine mammal hosts. The marine mammal reference strains Brucella pinnipedialis 12890 (harbour seal, Phoca vitulina) and Brucella ceti 12891 (harbour porpoise, Phocoena phocoena) were included in genus Brucella in 2007, however, their pathogenicity in the mouse model is pending. Herein this is evaluated in BALB/c mice with Brucella suis 1330 as a control. Both marine mammal strains were attenuated, however, B. ceti was present at higher levels than B. pinnipedialis in blood, spleen and liver throughout the infection, in addition B. suis and B. ceti were isolated from brains and faeces at times with high levels of bacteraemia. In B. suis-infected mice serum cytokines peaked at day 7. In B. pinnipedialis-infected mice, levels were similar, but peaked predominantly at day 3 and an earlier peak in spleen weight likewise implied an earlier response. The inflammatory response induced pathology in the spleen and liver. In B. ceti-infected mice, most serum cytokine levels were comparable to those in uninfected mice, consistent with a limited inflammatory response, which also was indicated by restricted spleen and liver pathology. Specific immune responses against all three strains were detected in vitro after stimulation of splenocytes from infected mice with the homologous heat-killed brucellae. Antibody responses in vivo were also induced by the three brucellae. The immunological pattern of B. ceti in combination with persistence in organs and limited pathology has heretofore not been described for other brucellae. These two marine mammal wildtype strains show an attenuated pattern in BALB/c mice only previously described for Brucella neotomea. PMID:26959235

  7. Marine Mammal Brucella Reference Strains Are Attenuated in a BALB/c Mouse Model

    PubMed Central

    Nymo, Ingebjørg H.; Arias, Maykel A.; Pardo, Julián; Álvarez, María Pilar; Alcaraz, Ana; Godfroid, Jacques; Jiménez de Bagüés, María Pilar

    2016-01-01

    Brucellosis is a zoonosis of worldwide distribution with numerous animal host species. Since the novel isolation of Brucella spp. from marine mammals in 1994 the bacteria have been isolated from various marine mammal hosts. The marine mammal reference strains Brucella pinnipedialis 12890 (harbour seal, Phoca vitulina) and Brucella ceti 12891 (harbour porpoise, Phocoena phocoena) were included in genus Brucella in 2007, however, their pathogenicity in the mouse model is pending. Herein this is evaluated in BALB/c mice with Brucella suis 1330 as a control. Both marine mammal strains were attenuated, however, B. ceti was present at higher levels than B. pinnipedialis in blood, spleen and liver throughout the infection, in addition B. suis and B. ceti were isolated from brains and faeces at times with high levels of bacteraemia. In B. suis-infected mice serum cytokines peaked at day 7. In B. pinnipedialis-infected mice, levels were similar, but peaked predominantly at day 3 and an earlier peak in spleen weight likewise implied an earlier response. The inflammatory response induced pathology in the spleen and liver. In B. ceti-infected mice, most serum cytokine levels were comparable to those in uninfected mice, consistent with a limited inflammatory response, which also was indicated by restricted spleen and liver pathology. Specific immune responses against all three strains were detected in vitro after stimulation of splenocytes from infected mice with the homologous heat-killed brucellae. Antibody responses in vivo were also induced by the three brucellae. The immunological pattern of B. ceti in combination with persistence in organs and limited pathology has heretofore not been described for other brucellae. These two marine mammal wildtype strains show an attenuated pattern in BALB/c mice only previously described for Brucella neotomea. PMID:26959235

  8. New strain of mouse hepatitis virus as the cause of lethal enteritis in infant mice.

    PubMed Central

    Hierholzer, J C; Broderson, J R; Murphy, F A

    1979-01-01

    A new strain of mouse hepatitis virus (MHV) was isolated from pooled gut suspensions from an epizootic of lethal enteritis in newborn mice. Negative-contrast electron microscopy showed an abundance of coronavirus particles in the intestinal contents and intestinal epithelium of moribund mice. We found no other virus in the epizootic. Dams seroconverted to MHV polyvalent antigen and to the agent isolated, but did not develop antibodies to other known mouse pathogens. Virus propagated in NCTC-1469 tissue culture produced enteric disease in suckling mice but not fatal diarrhea; the dams of these mice also developed antibodies to MHV and to the isolates. By complement fixation, single radial hemolysis, and quantal neutralization tests, we found the isolates antigenically most closely related to MHV-S, unilaterally related to MHV-JHM, and more distantly related to MHV-1, MHV-3, MHV-A59, and human coronavirus OC-43. We also studied cross-reactions among the murine and human coronaviruses in detail. Tissues of infected newborn mice were examined by light microscopy, thin-section electron microscopy, and frozen-section indirect immunofluorescence, revealing that viral antigen, virus particles, and pathological changes were limited to the intestinal tract. We have designated our isolates as MHV-S/CDC. Images PMID:222687

  9. Altered sensitivity to excitotoxic cell death and glutamate receptor expression between two commonly studied mouse strains

    PubMed Central

    Finn, Rozzy; Kovács, Attila D.; Pearce, David A.

    2011-01-01

    Alterations in glutamatergic synapse function have been implicated in the pathogenesis of many different neurological disorders including ischemia, epilepsy, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. While studying glutamate receptor function in juvenile Batten disease on the C57BL/6J and 129S6/SvEv mouse backgrounds, we noticed differences unlikely to be due to mutation difference alone. We report here that primary cerebellar granule cell cultures from C57BL/6J mice are more sensitive to NMDA-mediated cell death. Moreover, sensitivity to AMPA-mediated excitotoxicity is more variable and is dependent upon the treatment conditions and age of the cultures. Glutamate receptor surface expression levels examined in vitro by in situ ELISA and in vivo by Western blot in surface cross-linked cerebellar samples indicated that these differences in sensitivity are likely due to strain-dependent differences in cell surface receptor expression levels. We propose that differences in glutamate receptor expression and in excitotoxic vulnerability should be taken into consideration in the context of characterizing disease models on the C57BL/6J and 129S6/SvEv mouse backgrounds. PMID:20544821

  10. A mouse model of Acinetobacter baumannii-associated pneumonia using a clinically isolated hypervirulent strain.

    PubMed

    Harris, Greg; Kuo Lee, Rhonda; Lam, Christopher K; Kanzaki, Gregory; Patel, Girishchandra B; Xu, H Howard; Chen, Wangxue

    2013-08-01

    Acinetobacter baumannii is an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models of A. baumannii pneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model of A. baumannii pneumonia using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary A. baumannii infection and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, significant extrapulmonary dissemination, and severe bacteremia by 24 h postintranasal inoculation. Infected mice showed severe bronchopneumonia and dilatation and inflammatory cell infiltration in the perivascular space. More significantly, 100% of C57BL/6 and BALB/c mice succumbed to 10(8) CFU of LAC-4 inoculation within 48 h. When this model was used to assess the efficacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clinical signs and body weight loss. Moreover, intranasal immunization of mice with formalin-fixed LAC-4 protected 40% of mice from a lethal (100× 100% lethal dose) intraperitoneal challenge. Thus, this model offers a reproducible acute course of A. baumannii pneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines against A. baumannii pneumonia in humans. PMID:23689726

  11. Differences in GABA-induced chloride ion influx in brain of inbred mouse strains

    SciTech Connect

    Yu, O.; Chiu, T.H.; Rosenberg, H.C.

    1986-03-01

    Audiogenic seizure-susceptible (AS) mice (DBA2J) are a widely used model of epilepsy. The precise pathophysiology of this mouse strain is not fully understood. One of the proposed mechanisms was a difference in GABA/BZ receptor affinity and population from that of audiogenic seizure resistant (ASR) mice. This study attempted to determine the difference in function of GABA/BZ receptor between DBA2J (AS) and C57BL6J (ASR) mice by directly measuring the GABA-induced chloride ion (/sup 36/Cl/sup -/) influx in twice washed crude brain homogenates. /sup 36/Cl/sup -/ influx was terminated by ice-cold buffer and collected by filtration. A concentration range of 2-1000 ..mu..M GABA and two age-matched groups (20-22 days and 40-42 days) were used. GABA-induced /sup 36/Cl/sup -/ influx was dose-dependent, and brain homogenates from DBA2J mice (20-22 days) were less sensitive to GABA-induced Cl/sup -/ ion influx than C57BL6J mice at both age groups. However, in older DBA2J mice (40-42 days), the sensitivity to GABA was intermediate between that of the younger AS mice and the control ASR mice. No significant difference in basal influx of Cl/sup -/ was observed between age groups and mouse strains, nor was there any significant difference between 20-22 days old and 40-42 days old C57BL6J mice. In conclusion, this study had demonstrated a malfunction may recover with age.

  12. Paramagnetic Beads and Magnetically Mediated Strain Enhance Cardiomyogenesis in Mouse Embryoid Bodies

    PubMed Central

    Geuss, Laura R.; Wu, Douglas C.; Ramamoorthy, Divya; Alford, Corinne D.; Suggs, Laura J.

    2014-01-01

    Mechanical forces play an important role in proper embryologic development, and similarly such forces can directly impact pluripotency and differentiation of mouse embryonic stem cells (mESC) in vitro. In addition, manipulation of the embryoid body (EB) microenvironment, such as by incorporation of microspheres or microparticles, can similarly influence fate determination. In this study, we developed a mechanical stimulation regimen using permanent neodymium magnets to magnetically attract cells within an EB. Arginine-Glycine-Aspartic Acid (RGD)-conjugated paramagnetic beads were incorporated into the interior of the EBs during aggregation, allowing us to exert force on individual cells using short-term magnetization. EBs were stimulated for one hour at different magnetic field strengths, subsequently exerting a range of force intensity on the cells at different stages of early EB development. Our results demonstrated that following exposure to a 0.2 Tesla magnetic field, ESCs respond to magnetically mediated strain by activating Protein Kinase A (PKA) and increasing phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression. The timing of stimulation can also be tailored to guide ESC differentiation: the combination of bone morphogenetic protein 4 (BMP4) supplementation with one hour of magnetic attraction on Day 3 enhances cardiomyogenesis by increasing contractile activity and the percentage of sarcomeric α-actin-expressing cells compared to control samples with BMP4 alone. Interestingly, we also observed that the beads alone had some impact on differentiation by increasingly slightly, albeit not significantly, the percentage of cardiomyocytes. Together these results suggest that magnetically mediated strain can be used to enhance the percentage of mouse ESC-derived cardiomyocytes over current differentiation protocols. PMID:25501004

  13. INDUCTION OF DNA ADDUCTS, TUMORS, AND KI-RAS ONCOGENE MUTATIONS IN STRAIN A/J MOUSE LUNG BY IP. ADMINISTRATION OF DIBENZ[A,H]ANTHRACENE

    EPA Science Inventory

    Induction of DNA adducts, tumors, and Ki-ras oncogene mutations in strain AlJ mouse lung by ip. administration of dibenz[a,h]anthracene

    Previous studies of polycyclic aromatic hydrocarbon (P AH) induced lung tumors in the strain NJ mouse model system have demonstrated qua...

  14. Complete Genome Sequence of Turicibacter sp. Strain H121, Isolated from the Feces of a Contaminated Germ-Free Mouse.

    PubMed

    Auchtung, T A; Holder, M E; Gesell, J R; Ajami, N J; Duarte, R T D; Itoh, K; Caspi, R R; Petrosino, J F; Horai, R; Zárate-Bladés, C R

    2016-01-01

    Turicibacterbacteria are commonly detected in the gastrointestinal tracts and feces of humans and animals, but their phylogeny, ecological role, and pathogenic potential remain unclear. We present here the first complete genome sequence ofTuricibactersp. strain H121, which was isolated from the feces of a mouse line contaminated following germ-free derivation. PMID:27013036

  15. Complete Genome Sequence of Turicibacter sp. Strain H121, Isolated from the Feces of a Contaminated Germ-Free Mouse

    PubMed Central

    Auchtung, T. A.; Holder, M. E.; Gesell, J. R.; Ajami, N. J.; Duarte, R. T. D.; Itoh, K.; Caspi, R. R.; Petrosino, J. F.; Horai, R.

    2016-01-01

    Turicibacter bacteria are commonly detected in the gastrointestinal tracts and feces of humans and animals, but their phylogeny, ecological role, and pathogenic potential remain unclear. We present here the first complete genome sequence of Turicibacter sp. strain H121, which was isolated from the feces of a mouse line contaminated following germ-free derivation. PMID:27013036

  16. TRPV1 expression level in isolectin B₄-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity.

    PubMed

    Ono, Kentaro; Ye, Yi; Viet, Chi T; Dang, Dongmin; Schmidt, Brian L

    2015-05-01

    Differential thermal nociception across inbred mouse strains has genetic determinants. Thermal nociception is largely attributed to the heat/capsaicin receptor transient receptor potential vanilloid 1 (TRPV1); however, the contribution of this channel to the genetics of thermal nociception has not been revealed. In this study we compared TRPV1 expression levels and electrophysiological properties in primary sensory neurons and thermal nociceptive behaviors between two (C57BL/6 and BALB/c) inbred mouse strains. Using immunofluorescence and patch-clamp physiology methods, we demonstrated that TRPV1 expression was significantly higher in isolectin B4 (IB4)-positive trigeminal sensory neurons of C57BL/6 relative to BALB/c; the expression in IB4-negative neurons was similar between the strains. Furthermore, using electrophysiological cell classification (current signature method), we showed differences between the two strains in capsaicin sensitivity in IB4-positive neuronal cell types 2 and 13, which were previously reported as skin nociceptors. Otherwise electrophysiological membrane properties of the classified cell types were similar in the two mouse strains. In publicly available nocifensive behavior data and our own behavior data from the using the two mouse strains, C57BL/6 exhibited higher sensitivity to heat stimulation than BALB/c, independent of sex and anatomical location of thermal testing (the tail, hind paw, and whisker pad). The TRPV1-selective antagonist JNJ-17203212 inhibited thermal nociception in both strains; however, removing IB4-positive trigeminal sensory neurons with IB4-conjugated saporin inhibited thermal nociception on the whisker pad in C57BL/6 but not in BALB/c. These results suggest that TRPV1 expression levels in IB4-positive type 2 and 13 neurons contributed to differential thermal nociception in skin of C57BL/6 compared with BALB/c. PMID:25787958

  17. T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system.

    PubMed Central

    Sussman, M A; Shubin, R A; Kyuwa, S; Stohlman, S A

    1989-01-01

    Clearance of the neurotropic JHM strain of mouse hepatitis virus from the central nervous system was examined by the transfer of spleen cells from immunized donors. A T cell with the surface phenotype of Thy1.2+ CD4+ CD8- asialo-GM1+ Mac-1- was found to be necessary for viral clearance. The surface phenotype and adherence to nylon wool suggest that these cells are activated helper-inducer T cells. Adoptive transfer to congenic histocompatibility strains demonstrated the necessity for compatibility at the D locus of the major histocompatibility complex. The expression of the CD4 surface marker and the requirement for major histocompatibility complex class I were further studied by the transfer of cells to recipients treated with anti-CD4 or anti-CD8 monoclonal antibodies. Treatment of recipients with either the anti-CD8 or the anti-CD4 antibodies inhibited virus clearance from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system by CD8+ cells that recognize viral antigen in the context of the H-2Db gene product. PMID:2542613

  18. Lifetime Dependent Variation of Stress Hormone Metabolites in Feces of Two Laboratory Mouse Strains

    PubMed Central

    Kolbe, Thomas; Palme, Rupert; Tichy, Alexander; Rülicke, Thomas

    2015-01-01

    Non-invasive measurement of stress hormone metabolites in feces has become routine practice for the evaluation of distress and pain in animal experiments. Since metabolism and excretion of glucocorticoids may be variable, awareness and adequate consideration of influencing factors are essential for accurate monitoring of adrenocortical activity. Reference values are usually provided by baselines compiled prior to the experiment and by age matched controls. The comparison of stress hormone levels between animals of different ages or between studies looking at hormone levels at the beginning and at the end of a long term study might be biased by age-related effects. In this study we analyzed fecal corticosterone metabolites (FCM) during the lifetime of untreated female mice of the strains C57BL/6NCrl and Crl:CD1. For this purpose feces for each individual mouse were collected every two months over a period of 24 hours, at intervals of four hours, until the age of 26 months. Results of the study revealed that age of the animals had a significant impact on the level and circadian rhythm of stress hormone metabolites. Furthermore, long-term observation of mice revealed a strain specific excretion profile of FCM influenced by strong seasonal variability. PMID:26284365

  19. Age- and Strain- Dependent Influences of Morphine on Mouse Social Investigation Behavior

    PubMed Central

    Kennedy, Bruce C.; Panksepp, Jules B.; Wong, Jenny C.; Krause, Emily J.; Lahvis, Garet P.

    2011-01-01

    Opioid-coded neural circuits play a substantial role in how individuals respond to drugs of abuse, and most individuals begin using such drugs during adolescence and within a social context. Several studies indicate that adolescent mice exhibit a heightened sensitivity to the effects of morphine, the prototypical opiate drug, when compared with adults, but it is unclear whether these developmental differences are related to aspects of motivated behavior. Moreover, exposure to opioids within the rodent brain can alter the expression of social behavior, yet little is known about whether this relationship changes as a function of development or genetic variation. In this study, we conducted a series of experiments to characterize the relationship between genetic background, adolescent development and morphine-induced changes in mouse social investigation (SI). At two time-points during adolescent development (postnatal day [PD] 25 and 45), social interactions of test mice of the gregarious C57BL/6J (B6) strain were more tolerant to the suppressive effects of morphine (ED50 = 0.97 and 2.17 mg/kg morphine, respectively) than test mice from the less social BALB/cJ (BALB) strain (ED50 = 0.61 and 0.91 mg/kg morphine, respectively). By contrast, this strain-dependent difference was not evident among adult mice on PD 90 (ED50 = 1.07 and 1.41 mg/kg morphine for BALB and B6 mice, respectively). An additional experiment demonstrated that the ability of morphine to alter social responsiveness was not directly related to drug-induced changes in locomotor behavior. Finally, administration of morphine to stimulus mice on PD 25 reduced social interaction of test mice only when individuals were from the B6 genetic background. Overall, these results indicate that alterations in endogenous opioid systems are related to changes in SI that occur during adolescence and that morphine administration may mimic the rewarding nature of SI. PMID:21358324

  20. Ethnic and Mouse Strain Differences in Central Corneal Thickness and Association with Pigmentation Phenotype

    PubMed Central

    Dimasi, David P.; Hewitt, Alex W.; Kagame, Kenneth; Ruvama, Sam; Tindyebwa, Ludovica; Llamas, Bastien; Kirk, Kirsty A.; Mitchell, Paul; Burdon, Kathryn P.; Craig, Jamie E.

    2011-01-01

    The cornea is a transparent structure that permits the refraction of light into the eye. Evidence from a range of studies indicates that central corneal thickness (CCT) is strongly genetically determined. Support for a genetic component comes from data showing significant variation in CCT between different human ethnic groups. Interestingly, these studies also appear to show that skin pigmentation may influence CCT. To validate these observations, we undertook the first analysis of CCT in an oculocutaneous albinism (OCA) and Ugandan cohort, populations with distinct skin pigmentation phenotypes. There was a significant difference in the mean CCT of the OCA, Ugandan and Australian-Caucasian cohorts (Ugandan: 517.3±37 µm; Caucasian: 539.7±32.8 µm, OCA: 563.3±37.2 µm; p<0.001). A meta-analysis of 53 studies investigating the CCT of different ethnic groups was then performed and demonstrated that darker skin pigmentation is associated with a thinner CCT (p<0.001). To further verify these observations, we measured CCT in 13 different inbred mouse strains and found a significant difference between the albino and pigmented strains (p = 0.008). Specific mutations within the melanin synthesis pathway were then investigated in mice for an association with CCT. Significant differences between mutant and wild type strains were seen with the nonagouti (p<0.001), myosin VA (p<0.001), tyrosinase (p = 0.025) and tyrosinase related protein (p = 0.001) genes. These findings provide support for our hypothesis that pigmentation is associated with CCT and identifies pigment-related genes as candidates for developmental determination of a non-pigmented structure. PMID:21853026

  1. Variation and genetic control of gene expression in primary immunocytes across inbred mouse strains.

    PubMed

    Mostafavi, Sara; Ortiz-Lopez, Adriana; Bogue, Molly A; Hattori, Kimie; Pop, Cristina; Koller, Daphne; Mathis, Diane; Benoist, Christophe

    2014-11-01

    To determine the breadth and underpinning of changes in immunocyte gene expression due to genetic variation in mice, we performed, as part of the Immunological Genome Project, gene expression profiling for CD4(+) T cells and neutrophils purified from 39 inbred strains of the Mouse Phenome Database. Considering both cell types, a large number of transcripts showed significant variation across the inbred strains, with 22% of the transcriptome varying by 2-fold or more. These included 119 loci with apparent complete loss of function, where the corresponding transcript was not expressed in some of the strains, representing a useful resource of "natural knockouts." We identified 1222 cis-expression quantitative trait loci (cis-eQTL) that control some of this variation. Most (60%) cis-eQTLs were shared between T cells and neutrophils, but a significant portion uniquely impacted one of the cell types, suggesting cell type-specific regulatory mechanisms. Using a conditional regression algorithm, we predicted regulatory interactions between transcription factors and potential targets, and we demonstrated that these predictions overlap with regulatory interactions inferred from transcriptional changes during immunocyte differentiation. Finally, comparison of these and parallel data from CD4(+) T cells of healthy humans demonstrated intriguing similarities in variability of a gene's expression: the most variable genes tended to be the same in both species, and there was an overlap in genes subject to strong cis-acting genetic variants. We speculate that this "conservation of variation" reflects a differential constraint on intraspecies variation in expression levels of different genes, either through lower pressure for some genes, or by favoring variability for others. PMID:25267973

  2. Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain

    PubMed Central

    Hefner, Kathryn; Whittle, Nigel; Juhasz, Jaynann; Norcross, Maxine; Karlsson, Rose-Marie; Saksida, Lisa M.; Bussey, Timothy J.; Singewald, Nicolas; Holmes, Andrew

    2008-01-01

    Fear extinction is a form of new learning that results in the inhibition of conditioned fear. Trait deficits in fear extinction are a risk factor for anxiety disorders. There are few examples of naturally-occurring animal models of impaired extinction. The present study compared fear extinction in a panel of inbred mouse strains. This strain survey revealed an impairment in fear extinction in 129/SvImJ (129S1). The phenotypic specificity of this deficit was evaluated by comparing 129S1 and C57BL/6J for one-trial and multi-trial fear conditioning, nociception, and extinction of conditioned taste aversion (CTA) and an appetitive instrumental response. 129S1 were tested for sensitivity to the extinction-facilitating effects of extended training, as well as D-cycloserine and yohimbine treatment. To elucidate the neural basis of impaired 129S1 fear extinction, c-Fos and Zif268 expression was mapped following extinction recall. Results showed that impaired fear extinction in 129S1 was unrelated to altered fear conditioning or nociception, and was dissociable from intact appetitive extinction. Yohimbine treatment facilitated extinction in 129S1, but neither extended extinction training nor D-cycloserine treatment improved 129S1 extinction. Following extinction recall, 129S1 showed reduced c-Fos and Zif268 expression in the infralimbic cortex and basolateral amygdala, and elevated c-Fos or Zif268 expression in central nucleus of the amygdala and medial paracapsular intercalated cell mass, relative to C57BL/6J. Collectively, these data demonstrate a deficit in fear extinction in 129S1 associated with a failure to properly engage corticolimbic extinction circuitry. This common inbred strain provides a novel model for studying impaired fear extinction in anxiety disorders. PMID:18685032

  3. Cyclic mechanical strain maintains Nanog expression through PI3K/Akt signaling in mouse embryonic stem cells

    SciTech Connect

    Horiuchi, Rie; Akimoto, Takayuki; Hong, Zhang; Ushida, Takashi

    2012-08-15

    Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17 Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling. -- Highlights: Black-Right-Pointing-Pointer The expression of Nanog, which is an essential regulator of 'stemness' was reduced during embryonic stem (ES) cell differentiation. Black-Right-Pointing-Pointer Cyclic mechanical strain attenuated the reduction of Nanog expression. Black-Right-Pointing-Pointer Cyclic mechanical strain promoted PI3K-Akt signaling and mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor and an inhibitor of actin polymerization.

  4. Cerebellar protein expression in three different mouse strains and their relevance for motor performance.

    PubMed

    Pollak, Daniela; Weitzdoerfer, Rachel; Yang, Yae-Won; Prast, Helmut; Hoeger, Harald; Lubec, Gert

    2005-01-01

    The present study uses a proteomic approach to link motor function to cerebellar protein expression in 129X1/SvJ, C57BL/6J and nNOS WT mice. Poor performance on the Rota rod, the standard test for motor coordination, was detected in 129X1/SvJ mice. No gross impairments of neurological, cognitive and behavioural functions were observed. Identification and quantification of 48 proteins revealed reduced expression of calbindin, septin 5 and syntaxin binding protein 1 in 129X1/SvJ. In nNos WT glucose-6-phosphate 1 dehydrogenase X was decreased whereas dihydropyrimidinase-related protein-4 was increased. In C57BL/6J stress-70 protein, alpha enolase, NAD-dependent deacetylase sirtuin 2, septin 2, dihydropyrimidinase-related protein-2 and brain derived neurotrophic factor showed elevated levels. Neurological examination, Rota rod test, Morris Water Maze, Multiple-T-Maze, Open field and Elevated plus-maze were employed to study motor, cognitive and behavioural function. Mice were sacrificed and cerebellar tissue was homogenized. Proteins were extracted and separated on two-dimensional gel electrophoresis with subsequent in-gel digestion followed by mass spectrometrical analysis of peptides (MALDI-TOF/TOF-TOF). Quantification of spots was carried out by specific software. A strong association of impaired motor function with altered cerebellar protein expression of calbindin, septin 5 and syntaxin binding protein 1in 129X1/SvJ was observed and is in agreement with previous observations of motor deficiencies in a calbindin knock-out mouse. These results have to be taken into account when using 129X1/SvJ for biochemical, toxicological or gene targeting experiments as well as when studying the above-mentioned proteins or corresponding pathways and cascades in this mouse strain. PMID:15567512

  5. The SKG Mutation in ZAP-70 also Confers Arthritis Susceptibility in C57 Black Mouse Strains.

    PubMed

    Guerard, S; Boieri, M; Hultqvist, M; Holmdahl, R; Wing, K

    2016-07-01

    Various rodent models of arthritis are essential to dissect the full complexity of human rheumatoid arthritis (RA), a common autoimmune disease affecting joints. The SKG model of arthritis originates from a spontaneous mutation in ZAP-70 found in a BALB/c colony. This mutation affects T cell selection due to reduced TCR signalling, which allows leakage of self-reactive T cells from the thymus. To further expand the practical applicability of this unique model in arthritis research, we investigated the arthritogenicity of the SKG mutation in two common black mouse strains C57BL/6.Q and C57BL/10.Q and compared to BALB/c.Q. Mice retained the reduced TCR signalling characteristic of SKG.BALB/c mice, which leads to similar alteration in thymic selection. Importantly, mice also retained susceptibility to chronic arthritis after a single injection of mannan from Saccharomyces cerevisiae, with comparable prevalence and severity regardless of the genetic background. Further characterization of CD4(+) T cells revealed a similar bias towards IL-17 production and activated T cell phenotype in all SKG strains compared to respective wild type controls. Finally, transfer of SKG thymocytes conferred susceptibility to recipients, which confirm the intrinsic defect and pathogenicity of T cells. Overall, these results underline the strong impact that the W163C ZAP-70 mutation has on T cell-driven arthritis, and they support the use of the SKG model in black mice, which is useful for further investigations of this distinctive arthritis model to better understand autoimmunity. PMID:27040161

  6. Differential mouse-strain specific expression of Junctional Adhesion Molecule (JAM)-B in placental structures.

    PubMed

    Stelzer, Ina Annelies; Mori, Mayumi; DeMayo, Francesco; Lydon, John; Arck, Petra Clara; Solano, Maria Emilia

    2016-03-01

    The junctional adhesion molecule (JAM)-B, a member of the immunoglobulin superfamily, is involved in stabilization of interendothelial cell-cell contacts, formation of vascular tubes, homeostasis of stem cell niches and promotion of leukocyte adhesion and transmigration. In the human placenta, JAM-B protein is abundant and mRNA transcripts are enriched in first-trimester extravillous trophoblast in comparison to the villous trophoblast. We here aimed to elucidate the yet unexplored spatio-temporal expression of JAM-B in the mouse placenta. We investigated and semi-quantified JAM-B protein expression by immunohistochemistry in early post-implantation si tes and in mid- to late gestation placentae of various murine mating combinations. Surprisingly, the endothelium of the placental labyrinth was devoid of JAM-B expression. JAM-B was mainly present in spongiotrophoblast cells of the junctional zone, as well as in the fetal vessels of the chorionic plate, the umbilical cord and in maternal myometrial smooth muscle. We observed a strain-specific placental increase of JAM-B protein expression from mid- to late gestation in Balb/c-mated C57BL/6 females, which was absent in DBA/2J-mated Balb/c females. Due to the essential role of progesterone during gestation, we further assessed a possible modulation of JAM-B in mid-gestational placentae deficient in the progesterone receptor (Pgr(-/-)) and observed an increased expression of JAM-B in Pgr(-/-) placentae, compared to Pgr(+/+) tissue samples. We propose that JAM-B is an as yet underappreciated trophoblast lineage-specific protein, which is modulated via the progesterone receptor and shows unique strain-specific kinetics. Future work is needed to elucidate its possible contribution to placental processes necessary to ensuring its integrity, ultimately facilitating placental development and fetal growth. PMID:26914234

  7. Reliable sex and strain discrimination in the mouse vomeronasal organ and accessory olfactory bulb.

    PubMed

    Tolokh, Illya I; Fu, Xiaoyan; Holy, Timothy E

    2013-08-21

    Animals modulate their courtship and territorial behaviors in response to olfactory cues produced by other animals. In rodents, detecting these cues is the primary role of the accessory olfactory system (AOS). We sought to systematically investigate the natural stimulus coding logic and robustness in neurons of the first two stages of accessory olfactory processing, the vomeronasal organ (VNO) and accessory olfactory bulb (AOB). We show that firing rate responses of just a few well-chosen mouse VNO or AOB neurons can be used to reliably encode both sex and strain of other mice from cues contained in urine. Additionally, we show that this population code can generalize to new concentrations of stimuli and appears to represent stimulus identity in terms of diverging paths in coding space. Together, the results indicate that firing rate code on the temporal order of seconds is sufficient for accurate classification of pheromonal patterns at different concentrations and may be used by AOS neural circuitry to discriminate among naturally occurring urine stimuli. PMID:23966710

  8. Identification of sdiA-regulated genes in a mouse commensal strain of Enterobacter cloacae

    PubMed Central

    Sabag-Daigle, Anice; Dyszel, Jessica L.; Gonzalez, Juan F.; Ali, Mohamed M.; Ahmer, Brian M. M.

    2015-01-01

    Many bacteria determine their population density using quorum sensing. The most intensively studied mechanism of quorum sensing utilizes proteins of the LuxI family to synthesize a signaling molecule of the acylhomoserine lactone (AHL) type, and a protein of the LuxR family to bind AHL and regulate transcription. Genes regulated by quorum sensing often encode functions that are most effective when a group of bacteria are working cooperatively (e.g., luminescence, biofilm formation, host interactions). Bacteria in the Escherichia, Salmonella, Klebsiella, and Enterobacter genera do not encode an AHL synthase but they do encode an AHL receptor of the LuxR family, SdiA. Instead of detecting their own AHL synthesis, these organisms use SdiA to detect the AHLs synthesized by other bacterial species. In this study, we used a genetic screen to identify AHL-responsive genes in a commensal Enterobacter cloacae strain that was isolated from a laboratory mouse. The genes include a putative type VI secretion system, copA (a copper transporter), and fepE (extends O-antigen chain length). A new transposon mutagenesis strategy and suicide vectors were used to construct an sdiA mutant of E. cloacae. The AHL-responsiveness of all fusions was entirely sdiA-dependent, although some genes were regulated by sdiA in the absence of AHL. PMID:26075189

  9. Comparative pathogenicity of Coxsackievirus A16 circulating and noncirculating strains in vitro and in a neonatal mouse model.

    PubMed

    Huang, L; Liu, X; Li, J L; Chang, J L; Liu, G C; Yu, X F; Zhang, W Y

    2015-05-01

    An enterovirus 71 (EV71) vaccine for the prevention of hand, foot, and mouth disease (HMFD) is available, but it is not known whether the EV71 vaccine cross-protects against Coxsackievirus (CV) infection. Furthermore, although an inactivated circulating CVA16 Changchun 024 (CC024) strain vaccine candidate is effective in newborn mice, the CC024 strain causes severe lesions in muscle and lung tissues. Therefore, an effective CV vaccine with improved pathogenic safety is needed. The aim of this study was to evaluate the in vivo safety and in vitro replication capability of a noncirculating CVA16 SHZH05 strain. The replication capacity of circulating CVA16 strains CC024, CC045, CC090 and CC163 and the noncirculating SHZH05 strain was evaluated by cytopathic effect in different cell lines. The replication capacity and pathogenicity of the CC024 and SHZH05 strains were also evaluated in a neonatal mouse model. Histopathological and viral load analyses demonstrated that the SHZH05 strain had an in vitro replication capacity comparable to the four CC strains. The CC024, but not the SHZH05 strain, became distributed in a variety of tissues and caused severe lesions and mortality in neonatal mice. The differences in replication capacity and in vivo pathogenicity of the CC024 and SHZH05 strains may result from differences in the nucleotide and amino acid sequences of viral functional polyproteins P1, P2 and P3. Our findings suggest that the noncirculating SHZH05 strain may be a safer CV vaccine candidate than the CC024 strain. PMID:25831207

  10. Spontaneous Staphylococcus xylosus Infection in Mice Deficient in NADPH Oxidase and Comparison with Other Laboratory Mouse Strains

    PubMed Central

    Gozalo, Alfonso S; Hoffmann, Victoria J; Brinster, Lauren R; Elkins, William R; Ding, Li; Holland, Steven M

    2010-01-01

    Staphylococcus xylosus typically is described as a nonpathogenic common inhabitant of rodent skin. Reports of S. xylosus as a primary pathogen in human and veterinary medicine are scarce. Here we report 37 cases, affecting 12 strains of laboratory mice, of spontaneous infections in which S. xylosus was isolated and considered to be the primary pathogen contributing to the death or need for euthanasia of the animal. Infection with S. xylosus was the major cause of death or euthanasia in 3 strains of mice deficient in the production of phagocyte superoxide due to defects in NADPH oxidase. NADPH-oxidase–deficient mice (n = 21) were most susceptible to spontaneous S. xylosus infections. The infections were characterized by abscesses and granulomas in soft tissues, with bacterial migration to internal organs (primarily regional lymph nodes and lungs and, to a lesser degree, muscle, bone, and meninges). In contrast, 9 strains of phagocyte-superoxide–producing mice (n = 16) also had S. xylosus infections, but these were largely confined to eyelids, ocular conjunctiva, and skin and rarely involved other tissues or organs. Because exhaustive bacterial culture and isolation may not be performed routinely from mouse abscesses, S. xylosus infections may be underdiagnosed. S. xylosus should be considered in the differential diagnosis in laboratory mice with abscesses and other skin lesions. This report expands the range of mouse strains and tissues and organs susceptible to spontaneous S. xylosus infection and compares the pathology among various mice strains. PMID:20819397

  11. Technical note: Milk composition in mice--methodological aspects and effects of mouse strain and lactation day.

    PubMed

    Görs, S; Kucia, M; Langhammer, M; Junghans, P; Metges, C C

    2009-02-01

    Analysis in individual mouse milk samples is restricted by small sample volumes and hindered by high fat contents. Miniaturized methods were developed for the analysis of dry matter (DM), crude fat, crude protein (CP), and lactose in individual samples of mouse milk and used to compare milk from the mouse strain DU6, the largest growth-selected mouse line worldwide, with unselected mice (CON) on lactation d 3, 14, and 18. Individual milk samples were collected by means of a self-constructed milking machine. Aliquots of 10 microL of milk were used to measure DM [coefficient of variation (CV) <2.1%], which was subsequently used to analyze nitrogen for calculation of CP (CV 2.7%). Crude fat was determined in 100 microL via a miniaturized Röse-Gottlieb method (CV 2.8%). An HPLC protocol was used to analyze lactose in 20 microL of diluted whey (CV 5.3%). The miniaturized methods gave similar results compared with conventional approaches. Homogenization was the most important factor affecting milk composition and its reproducibility. Milk storage at -20 degrees C had no effect on composition. Irrespective of the mouse strain, maximum values of 45.5% DM, 29.8% fat, and 12.7% CP were observed at d 14. The greatest lactose contents were found on d 18 (2.41%). Milk lactose concentration at d 3 was lower in DU6 (1.13 +/- 0.10%) than CON (1.67 +/- 0.18%). The method provides an accurate assessment of mouse milk composition. PMID:19164675

  12. Levels of dendritic cell populations and regulatory T cells vary significantly between two commonly used mouse strains.

    PubMed

    Vogelsang, Petra; Hovden, Arnt-Ove; Jonsson, Roland; Appel, Silke

    2009-12-01

    Dendritic cells (DC) are a heterogeneous group of professional antigen-presenting cells (APC) involved in both initiating immune responses and maintaining tolerance. Roughly, DC can be divided into plasmacytoid DC (pDC) and conventional DC (cDC). By controlling regulatory T cells (Treg), DC can influence the outcome of both immunity and autoimmunity. Since the use of mice as in vivo models became a practical tool for researchers studying pathological events in all kind of human diseases, we decided to compare levels of cDC, pDC and Treg in both spleen and blood between two inbred mouse strains. Here we show that two commonly used mouse strains, BALB/c and C57BL/10J mice, have significantly different levels of distinct CD11c(+)/CD4(-)/CD8a(+), CD11c(+)/CD4(+)/CD8a(-) and CD11c(+)/CD4(-)/CD8a(-) cDC populations, pDC and Treg. Therefore, we emphasize the importance of considering the proper model when comparing data sets from different mouse strains. PMID:19906196

  13. Comparative analysis of genetically engineered immunodeficient mouse strains as recipients for human myoblast transplantation.

    PubMed

    Silva-Barbosa, Suse D; Butler-Browne, Gillian S; Di Santo, James P; Mouly, Vincent

    2005-01-01

    The development of an optimized animal model for the in vivo analysis of human muscle cells remains an important goal in the search of therapy for muscular dystrophy. Here we examined the efficiency of human myoblast xenografts in three distinct immunodeficient mouse models. We found that different conditioning regimes used to provoke host muscle regeneration (i.e., cardiotoxin versus cryodamage) had a marked impact on xenograft success. Tibialis anterior muscle of Rag2-, Rag-/gammac-, and Rag-/gammac-/C5- mice was treated by cardiotoxin or cryodamage, submitted to enzymatic digestion, and analyzed by cytofluorometry to quantitate inflammatory cells. Human myoblasts were injected into pretreated muscles from immunodeficient recipients and the cell engraftment evaluated by immunocytochemistry, 4-8 weeks after transplantation. Donor cell differentiation and dispersion within the host muscles was also investigated. Host regeneration in cardiotoxin-treated mice was accompanied by a higher inflammatory cell infiltration when compared to that induced by cryodamage. Accordingly, when compared to the cardiotoxin group, more human myogenic cells were found after cryodamage. When the distinct immunodeficient mice were compared, we found that the alymphoid strain lacking the complement component C5 (Rag-/gammac-/C5- mice) was the most efficient host for human muscle xenografts, when compared with C5(+)Rag-/gammac- mice or Rag- mice. Our results demonstrate that cryolesion-conditioned muscles of Rag-/gammac-/C5- mice provide the best environment for long-term in vivo human myoblast differentiation, opening the way for a novel approach to study the pathophysiology of human muscle disorders. PMID:16285254

  14. A novel spontaneous mutation of BCAR3 results in extrusion cataracts in CF#1 mouse strain.

    PubMed

    Kondo, Tomohiro; Nakamori, Taketo; Nagai, Hiroaki; Takeshita, Ai; Kusakabe, Ken-Takeshi; Okada, Toshiya

    2016-10-01

    A substrain of mice originating from the CF#1 strain (an outbred colony) reared at Osaka Prefecture University (CF#1/lr mice) develops cataracts beginning at 4 weeks of age. Affected mice were fully viable and fertile and developed cataracts by 14 weeks of age. Histologically, CF#1/lr mice showed vacuolation of the lens cortex, swollen lens fibers, lens rupture and nuclear extrusion. To elucidate the mode of inheritance, we analyzed heterozygous mutant hybrids generated from CF#1/lr mice and wild-type BALB/c mice. None of the heterozygous mutants were affected, and the ratio of affected to unaffected mice was 1:3 among the offspring of the heterozygous mutants. For the initial genome-wide screening and further mapping, we used affected progeny of CF#1/lr × (CF#1/lr × BALB/c) mice. We concluded that the cataracts in CF#1/lr mice are inherited through an autosomal recessive mutation and that the mutant gene is located on mouse chromosome 3 between D3Mit79 and D3Mit216. In this region, we identified 8 genes associated with ocular disease. All 8 genes were sequenced and a novel point mutation (1 bp insertion of cytosine) in exon 7 of the Bcar3 gene was identified. This mutation produced a premature stop codon and a truncated protein. In conclusion, we have identified the first spontaneous mutation in the Bcar3 gene associated with lens extrusion cataracts. This novel cataract model may provide further knowledge of the molecular biology of cataractogenesis and the function of the BCAR3 protein. PMID:27364350

  15. Acute toxicity and cytotoxicity of Bacillus thuringiensis and Bacillus sphaericus strains on fish and mouse bone marrow.

    PubMed

    Grisolia, Cesar Koppe; Oliveira-Filho, Eduardo Cyrino; Ramos, Felipe Rosa; Lopes, Madaí Cruz; Muniz, Daphne Heloisa Freitas; Monnerat, Rose Gomes

    2009-01-01

    The insecticidal properties of delta-endotoxins from Bacillus thuringiensis (Bt) serotypes kurstaki and israelensis and crystal proteins of Bacillus sphaericus (Bs) serotype H5 have been used in insect control for decades. The availability of microbial toxins in biopesticides as well as in plants with incorporated protection has been increasing the concerns about biosafety. Acute toxicity to Danio rerio and cytotoxicity on mouse bone marrow cells and peripheral erythrocytes of Oreochromis niloticus were tested with Bt israelensis, Bt kurstaki and Bs H5 strains. The concentration and dose tested were 10(6) and 10(8) spores/ml, respectively. Neither lethality nor effects on mouse bone marrow were promoted by any strain. In necrosis-apoptosis study on peripheral erythrocytes of O. niloticus an increased frequency of necrotic cells caused by exposure to strains of B. thuringiensis was found. Exposure to B. sphaericus did not show cytotoxic effects in either tested system. None of the strains studied induced apoptosis in contrast with the chemical controls. PMID:18670879

  16. Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

    PubMed Central

    Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

    2014-01-01

    Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

  17. Multiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains.

    PubMed

    Taylor, B A; Wnek, C; Schroeder, D; Phillips, S J

    2001-02-01

    The inheritance of adiposity levels has been investigated in an intercross of the obese, diabetes-prone NZO and the small, lean SM mouse strains. Adiposity index (AI) was defined as the sum of four fat pad weights divided by body weight. DNA pools from fat and lean mice were analyzed with microsatellite variants to screen the genome for quantitative trait loci (QTLs) affecting AI. Ten significant QTLs affecting AI were identified on Chromosome (Chr) 1 (three loci), Chr 2, Chr 5 (two loci), Chr 6 (two loci), Chr 7, and Chr 17. Most of the QTLs appear to be novel. Several QTLs differentially affect specific fat depots. Thus, Chr 2 and Chr 7 QTLs affect gonadal more than inguinal fat, while the converse is true for the Chr 17 QTL. Gender influences the expression of several of the QTLs. For example, effects of the proximal Chr 1 QTL (Obq7) on AI appears to be primarily in males. The proximal AI QTL on Chr 6 (Obq13) maps near the neuropeptide Y (Npy) locus. Sequence analysis of the Npy gene revealed a 1-nucleotide deletion within a highly conserved portion of the 3' untranslated region in strain NZO. However, the deletion is polymorphic among mouse strains. Furthermore, lack of association between this same variant and AI in previously analyzed crosses raises doubt that it is the basis of Obq13. The present cross is the fourth in a series of intercrosses among 10 inbred strains arranged such that each strain is crossed with each adjacent strain within a circle. This design affords multiple opportunities to analyze each segregating QTL. PMID:11210195

  18. Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Liver Effects

    PubMed Central

    Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Shymonyak, Svitlana; Uehara, Takeki; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

    2014-01-01

    Trichloroethylene (TCE) is a widely used organic solvent. Although TCE is classified as carcinogenic to humans, substantial gaps remain in our understanding of inter-individual variability in TCE metabolism and toxicity, especially in the liver. We tested a hypothesis that amounts of oxidative metabolites of TCE in mouse liver are associated with liver-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione] in serum and liver, and various liver toxicity phenotypes. In sub-acute study, inter-strain variability in TCE metabolite amounts was observed in serum and liver. No induction of Cyp2e1 protein levels in liver was detected. Serum and liver levels of TCA and DCA were correlated with increased transcription of peroxisome proliferator-marker genes Cyp4a10 and Acox1, but not with degree of induction in hepatocellular proliferation. In sub-chronic study, serum and liver levels of oxidative metabolites gradually decreased over time despite continuous dosing. Liver protein levels of Cyp2e1, Adh and Aldh2 were unaffected by treatment with TCE. While the magnitude of induction of peroxisome proliferator-marker genes also declined, hepatocellular proliferation increased. This study offers a unique opportunity to provide a scientific data-driven rationale for some of the major assumptions in human health assessment of TCE. PMID:25424544

  19. A survey of airway responsiveness in 36 inbred mouse strains facilitates gene mapping studies and identification of quantitative trait loci

    PubMed Central

    Leme, Adriana S.; Williams, Laura K.; Tsaih, Shirng-Wern; Szatkiewicz, Jin P.; Verdugo, Ricardo; Paigen, Beverly; Shapiro, Steven D.

    2010-01-01

    Airway hyper-responsiveness (AHR) is a critical phenotype of human asthma and animal models of asthma. Other studies have measured AHR in nine mouse strains, but only six strains have been used to identify genetic loci underlying AHR. Our goals were to increase the genetic diversity of available strains by surveying 27 additional strains, to apply haplotype association mapping to the 36-strain survey, and to identify new genetic determinants for AHR. We derived AHR from the increase in airway resistance in females subjected to increasing levels of methacholine concentrations. We used haplotype association mapping to identify associations between AHR and haplotypes on chromosomes 3, 5, 8, 12, 13, and 14. And we used bioinformatics techniques to narrow the identified region on chromosome 13, reducing the region to 29 candidate genes, with 11 of considerable interest. Our combined use of haplotype association mapping with bioinformatics tools is the first study of its kind for AHR on these 36 strains of mice. Our analyses have narrowed the possible QTL genes and will facilitate the discovery of novel genes that regulate AHR in mice. PMID:20143096

  20. Quantification of Myocardial Strain at Early Systole in Mouse Heart: Restoration of Undeformed Tagging Grid with Single-Point HARP

    PubMed Central

    Li, Wei; Yu, Xin

    2010-01-01

    Purpose To develop accurate strain and torsion quantification method for the assessment of myocardial contraction in mice by MRI tagging. Materials and Methods Ventricular wall motion at baseline and during β-adrenergic stimulation was assessed in mice using MRI tagging. Myocardial strain and torsion were quantified using finite element analysis method. A harmonic phase (HARP) based method was developed for the restoration of undeformed taglines for more accurate calculation of myocardial wall strain and torsion. Results Myocardial deformation was observed at early systole (< 20 ms after QRS) both at baseline and during β-adrenergic stimulation. The HARP-based method allowed robust restoration of undeformed taglines that can be used as the reference in finite element analysis of the tagged images. Without such correction for myocardial deformation in the reference image, inaccuracy in strain quantification underestimated significant strain development at early systole in dobutamine-stimulated hearts. Conclusion The HARP-based method developed in the current study enabled automated restoration of undeformed taglines in mouse hearts, leading to more accurate calculation of myocardial wall strain and torsion during dobutamine stimulation. PMID:20815058

  1. Studies with pyrethroids (kadethrin and deltamethrin) and lindane in ethanol sensitive (LS) and insensitive (SS) mouse strains

    SciTech Connect

    Doherty, J.; Baker, R.C.; Deitrich, R. )

    1990-02-26

    Ethanol (E) sensitive (LS) and insensitive (SS) mouse strains are distinguished by their sleeping time to a given dose of E and the locus for this difference is at the level of the neuron. In attempts to understand the neuropharmacological basis of insecticide action and to further define the differences in these mouse lines, LS and SS mice were dosed with type I (kadethrine, K) and II (deltamethrin, D) pyrethroids and lindane (L). These compounds were selected because their proposed modes of action are on the Na+ channel (K and D) and/or the GABA receptor ionophore (D and L). No consistent differences in the effects of K, D or L in the SS and LS mouse lines were evident. In preliminary studies both SS and LS mice dosed with 50 or 100 {mu}g/brain of L (intracerebroventricularly) but not D slept much longer (2-3X) than when dosed with E alone, an effect opposite of that predicted from L's known excitatory action. These data indicate that as far as can be distinguished by pyrethroids and L, the Na+ channel and GABA receptor/ionophore complex are similar in both the LS and SS mouse lines.

  2. Strain Differences in Behavioral Inhibition in a Go/No-go Task Demonstrated Using 15 Inbred Mouse Strains

    PubMed Central

    Gubner, Noah R.; Wilhelm, Clare J.; Phillips, Tamara J.; Mitchell, Suzanne H.

    2012-01-01

    Background High levels of impulsivity have been associated with a number of substance abuse disorders including alcohol abuse. Research has not yet revealed whether these high levels predate the development of alcohol abuse. Methods The current study examined impulsivity in 15 inbred strains of mice (A/HeJ, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C57L/J, C58/J, CBA/J, DBA/1J, DBA/2J, NZB/B1NJ, PL/J, SJL/J, SWR/J, and 129P3/J) using a Go/No-go task, which was designed to measure a subject’s ability to inhibit a behavior. Numerous aspects of response to ethanol and other drugs of abuse have been examined in these strains. Results There were significant strain differences in the number of responses made during the No-go signal (false alarms) and the extent to which strains responded differentially during the Go and No-go signals (d′). The rate of responding prior to the cue did not differ among strains, although there was a statistically significant correlation between false alarms and precue responding that was not related to basal activity level. Interstrain correlations suggested that false alarms and rate of responding were associated with strain differences in ethanol-related traits from the published literature. Conclusions The results of this study do support a link between innate level of impulsivity and response to ethanol and are consistent with a genetic basis for some measures of behavioral inhibition. PMID:20491731

  3. Effects of Sulfamethizole and Amdinocillin against Escherichia coli Strains (with Various Susceptibilities) in an Ascending Urinary Tract Infection Mouse Model

    PubMed Central

    Kerrn, M. B.; Frimodt-Møller, N.; Espersen, F.

    2003-01-01

    Resistance to antibiotics used for the treatment of urinary tract infections (UTIs) is increasing worldwide. The impact of in vitro resistance on clinical outcome in UTIs requires further study, since most studies of both humans and animals have evaluated only the efficacy of antibiotics toward bacteria susceptible in vitro. We were interested in evaluating the relationship between the in vitro antibacterial effect and the in vivo efficacy after antibiotic treatment. We simulated a natural ascending UTI by use of the ascending UTI mouse model and used Escherichia coli strains with various susceptibilities to amdinocillin (mecillinam) and sulfamethizole. Mice were treated for 3 days with antibiotic doses approximating human urinary tract concentrations after a standard oral dose. For a susceptible strain (MIC, 0.5 μg/ml) and a resistant strain (MIC, 128 μg/ml), respectively, there were significant reductions in bacterial counts in the urine, bladder, and kidneys after treatment with amdinocillin, whereas for a strain for which the MIC was 16 μg/ml, there was a significant reduction in bacterial counts in the kidneys only (P < 0.05). Treatment with sulfamethizole resulted in a significant reduction in bacterial counts in all samples from a susceptible strain (MIC, 128 μg/ml) and a resistant strain (MIC, 512 μg/ml). Infection with a sulII gene-positive strain (MIC, >2,048 μg/ml) could not be treated with sulfamethizole, as no effect could be demonstrated in the urine, bladder, or kidneys. For amdinocillin, there was no clear-cut relationship between the in vitro susceptibility and the in vivo outcome, while for sulfamethizole, we found a relationship between the MIC for the strain and the effect in the urinary tract. PMID:12604534

  4. Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains.

    PubMed

    Ma, Liang; Chan, Kwok-Wah; Trendell-Smith, Nigel J; Wu, Adrian; Tian, Lina; Lam, Audrey C; Chan, Albert K; Lo, Chi-Kin; Chik, Stanley; Ko, King-Hung; To, Christina K W; Kam, Siu-Kee; Li, Xiao-Song; Yang, Cui-Hong; Leung, Suet Yi; Ng, Mun-Hon; Stott, David I; MacPherson, G Gordon; Huang, Fang-Ping

    2005-11-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown etiology. Anti-double-stranded (ds) DNA antibodies are a classic hallmark of the disease, although the mechanism underlying their induction remains unclear. We demonstrate here that, in both lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DC) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident, however, only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-gamma and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupus-prone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis. PMID:16224814

  5. A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus

    SciTech Connect

    Zhang Shuliu; Li Li; Woodson, Sara E.; Huang, Claire Y.-H.; Kinney, Richard M.; Barrett, Alan D.T. ||||; Beasley, David W.C. |||. E-mail: d.beasley@utmb.edu

    2006-09-15

    Substitutions were engineered individually and in combinations at the fusion loop, receptor-binding domain and a stem-helix structure of the envelope protein of a West Nile virus strain, NY99, and their effects on mouse virulence and presentation of epitopes recognized by monoclonal antibodies (MAbs) were assessed. A single substitution within the fusion loop (L107F) attenuated mouse neuroinvasiveness of NY99. No substitutions attenuated NY99 neurovirulence. The L107F mutation also abolished binding of a non-neutralizing MAb, 3D9, whose epitope had not been previously identified. MAb 3D9 was subsequently shown to be broadly cross-reactive with other flaviviruses, consistent with binding near the highly conserved fusion loop.

  6. Effects of cell source, mouse strain, and immunosuppressive treatment on production of virulent and attenuated murine cytomegalovirus.

    PubMed Central

    Selgrade, M K; Nedrud, J G; Collier, A M; Gardner, D E

    1981-01-01

    Murine cytomegalovirus pools from various in vitro and in vivo sources were compared for virulence in suckling mice in an effort to identify the conditions which were necessary for the production of virulent and attenuated viruses. Virus passaged in tracheal ring and salivary gland organ cultures, where virus is produced primarily by epithelial cells, was even more attenuated than virus passaged in mouse embryo fibroblasts. The attenuation observed after passage in all three of these in vitro systems did not appear to be due to defective interfering particles. We also found that virus produced in vivo in salivary glands became attenuated with time after infection. Virus harvested from salivary glands 5 to 6 weeks after infection was highly attenuated compared with both salivary gland-passaged virus harvested 2 to 3 weeks after infection and tissue culture-passaged virus. The attenuation of salivary gland-passaged virus with time was reversed when animals were treated with cyclophosphamide before the virus was harvested. A comparison of virus pools harvested from susceptible and resistant mouse strains indicated that the mouse strain had little effect on the virulence of the virus produced. When the various sources of virus tested in this study were ranked in terms of the virulence of the virus produced, salivary glands in intact mice either 2 to 3 weeks after infection or after cyclophosphamide treatment produced the most virulent virus, followed by mouse embryo fibroblast cultures, tracheal ring and salivary gland organ cultures, and, finally, salivary glands in intact mice 5 to 6 weeks after infection. PMID:6270000

  7. A Mouse Strain Where Basal Connective Tissue Growth Factor Gene Expression Can Be Switched from Low to High

    PubMed Central

    Doherty, Heather E.; Kim, Hyung-Suk; Hiller, Sylvia; Sulik, Kathleen K.; Maeda, Nobuyo

    2010-01-01

    Connective tissue growth factor (CTGF) is a signaling molecule that primarily functions in extracellular matrix maintenance and repair. Increased Ctgf expression is associated with fibrosis in chronic organ injury. Studying the role of CTGF in fibrotic disease in vivo, however, has been hampered by perinatal lethality of the Ctgf null mice as well as the limited scope of previous mouse models of Ctgf overproduction. Here, we devised a new approach and engineered a single mutant mouse strain where the endogenous Ctgf-3′ untranslated region (3′UTR) was replaced with a cassette containing two 3′UTR sequences arranged in tandem. The modified Ctgf allele uses a 3′UTR from the mouse FBJ osteosarcoma oncogene (c-Fos) and produces an unstable mRNA, resulting in 60% of normal Ctgf expression (Lo allele). Upon Cre-expression, excision of the c-Fos-3′UTR creates a transcript utilizing the more stable bovine growth hormone (bGH) 3′UTR, resulting in increased Ctgf expression (Hi allele). Using the Ctgf Lo and Hi mutants, and crosses to a Ctgf knockout or Cre-expressing mice, we have generated a series of strains with a 30-fold range of Ctgf expression. Mice with the lowest Ctgf expression, 30% of normal, appear healthy, while a global nine-fold overexpression of Ctgf causes abnormalities, including developmental delay and craniofacial defects, and embryonic death at E10-12. Overexpression of Ctgf by tamoxifen-inducible Cre in the postnatal life, on the other hand, is compatible with life. The Ctgf Lo-Hi mutant mice should prove useful in further understanding the function of CTGF in fibrotic diseases. Additionally, this method can be used for the production of mouse lines with quantitative variations in other genes, particularly with genes that are broadly expressed, have distinct functions in different tissues, or where altered gene expression is not compatible with normal development. PMID:20877562

  8. Establishment of c-myc-immortalized Kupffer cell line from a C57BL/6 mouse strain.

    PubMed

    Kitani, Hiroshi; Sakuma, Chisato; Takenouchi, Takato; Sato, Mitsuru; Yoshioka, Miyako; Yamanaka, Noriko

    2014-01-01

    We recently demonstrated in several mammalian species, a novel procedure to obtain liver-macrophages (Kupffer cells) in sufficient numbers and purity using a mixed primary culture of hepatocytes. In this study, we applied this method to the C57BL/6 mouse liver and established an immortalized Kupffer cell line from this mouse strain. The hepatocytes from the C57BL/6 adult mouse liver were isolated by a two-step collagenase perfusion method and cultured in T25 culture flasks. Similar to our previous studies, the mouse hepatocytes progressively changed their morphology into a fibroblastic appearance after a few days of culture. After 7-10 days of culture, Kupffer-like cells, which were contaminants in the hepatocyte fraction at the start of the culture, actively proliferated on the mixed fibroblastic cell sheet. At this stage, a retroviral vector containing the human c-myc oncogene and neomycin resistance gene was introduced into the mixed culture. Gentle shaking of the culture flask, followed by the transfer and brief incubation of the culture supernatant, resulted in a quick and selective adhesion of Kupffer cells to a plastic dish surface. After selection with G418 and cloning by limiting dilutions, a clonal cell line (KUP5) was established. KUP5 cells displayed typical macrophage morphology and were stably passaged at 4-5 days intervals for more than 5 months, with a population doubling time of 19 h. KUP5 cells are immunocytochemically positive for mouse macrophage markers, such as Mac-1, F4/80. KUP5 cells exhibited substantial phagocytosis of polystyrene microbeads and the release of inflammatory cytokines upon lipopolysaccharide stimulation. Taken together, KUP5 cells provide a useful means to study the function of Kupffer cells in vitro. PMID:25379377

  9. 1 + 1 = 3: Development and validation of a SNP-based algorithm to identify genetic contributions from three distinct inbred mouse strains.

    PubMed

    Gorham, James D; Ranson, Matthew S; Smith, Janebeth C; Gorham, Beverly J; Muirhead, Kristen-Ashley

    2012-12-01

    State-of-the-art, genome-wide assessment of mouse genetic background uses single nucleotide polymorphism (SNP) PCR. As SNP analysis can use multiplex testing, it is amenable to high-throughput analysis and is the preferred method for shared resource facilities that offer genetic background assessment of mouse genomes. However, a typical individual SNP query yields only two alleles (A vs. B), limiting the application of this methodology to distinguishing contributions from no more than two inbred mouse strains. By contrast, simple sequence length polymorphism (SSLP) analysis yields multiple alleles but is not amenable to high-throughput testing. We sought to devise a SNP-based technique to identify donor strain origins when three distinct mouse strains potentially contribute to the genetic makeup of an individual mouse. A computational approach was used to devise a three-strain analysis (3SA) algorithm that would permit identification of three genetic backgrounds while still using a binary-output SNP platform. A panel of 15 mosaic mice with contributions from BALB/c, C57Bl/6, and DBA/2 genetic backgrounds was bred and analyzed using a genome-wide SNP panel using 1449 markers. The 3SA algorithm was applied and then validated using SSLP. The 3SA algorithm assigned 85% of 1449 SNPs as informative for the C57Bl/6, BALB/c, or DBA/2 backgrounds, respectively. Testing the panel of 15 F2 mice, the 3SA algorithm predicted donor strain origins genome-wide. Donor strain origins predicted by the 3SA algorithm correlated perfectly with results from individual SSLP markers located on five different chromosomes (n=70 tests). We have established and validated an analysis algorithm based on binary SNP data that can successfully identify the donor strain origins of chromosomal regions in mice that are bred from three distinct inbred mouse strains. PMID:23204929

  10. An edited linkage map for the AXB and BXA recombinant inbred mouse strains.

    PubMed

    Sampson, S B; Higgins, D C; Elliot, R W; Taylor, B A; Lueders, K K; Koza, R A; Paigen, B

    1998-09-01

    We have updated the history of the AXB and BXA recombinant inbred (RI) strains, typed additional loci, and edited the AXB, BXA RI database. Thirteen of the original 51 AXB and BXA RI strains are either extinct or genetically contaminated, leaving 33 living strains available from The Jackson Laboratory. However, we found a high degree of similarity among three sets of strains, indicating that these strains are not independent, which leaves 27 independent RI strains in the set. Accordingly, we modified the database by combining the AXB and BXA RI sets and eliminating strains that were genetically contaminated or extinct with no available DNA. We added 92 newly typed loci, retyped some questionable genotypings, and removed loci with excessive double crossovers or an insufficient number of typed strains. The edited strain distribution pattern (SDP) is available on the World Wide Web (WWW) (http://www. informatics.jax.org/riset.html) and now includes over 700 loci. Each locus is linked to adjacent loci with a LOD score of at least 3.0 with a few described exceptions. We also carried out a second editing designed for the analysis of quantitative trait loci by deleting extinct strains and loci with identical SDPs; this edited database is also available on the WWW. PMID:9716653

  11. Reproducibility of toxicity test data as a function of mouse strain, animal lot, and operator. [for bisphenol A polycarbonate

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Furst, A.

    1978-01-01

    The toxicity screening test method developed at the University of San Francisco was evaluated for reproducibility. The variables addressed were strain of mouse, lot of animals, and operator. There was a significant difference in response between Swiss Webster mice and ICR mice, with the latter exhibiting greater resistance. These two strains of mice are not interchangeable in this procedure. Variation between individual animals was significant and unavoidable. In view of this variation, between-lot and between-operator variations appear to have no practical significance. The significant variation between individual animals stresses the need for average values based on at least four animals, and preferably values based on at least two experiments and eight animals. Efforts to compare materials should be based on the evaluation of relatively simple responses using substantial numbers of animals, rather than on elaborate evaluation of single animals

  12. A-to-I pre-mRNA editing of the serotonin 2C receptor: comparisons among inbred mouse strains.

    PubMed

    Du, Yunzhi; Davisson, Muriel T; Kafadar, Karen; Gardiner, Katheleen

    2006-11-01

    The serotonin receptor 5HT2CR pre-mRNA is subject to adenosine deamination (RNA editing) at five residues located within a 15 nucleotide stretch of the coding region. Such changes of adenosine to inosine (A-to-I) can produce 32 mRNA variants, encoding 24 different protein isoforms, some of which vary in biochemical and pharmacological properties. Because serotonin mediates diverse neurological processes relevant to behavior and because inbred mouse strains vary in their responses to tests of learning and behavior, we have examined the A-to-I editing patterns of the 5HT2CR mRNA in whole brains from eight mouse strains. By sequencing approximately 100 clones from individual mice, we generated detailed information on levels of editing at each site and patterns of editing that identify a total of 28 mRNA and 20 protein isoforms. Significant differences between individuals from different strains were found in total editing frequency, in the proportion of transcripts with 1 and 4 edited sites, in editing frequency at the A, B, E and D sites, in amino acid frequencies at positions 157 and 161, and in subsets of major protein isoforms. Primer extension assays were used to show that individuals within strains (six C3H.B-+rd1 and four 129SvImrJ) displayed no significant differences in any feature. These findings suggest that genetic background contributes to subtle variation in 5HT2CR mRNA editing patterns which may have consequences for pharmacological treatments and behavioral testing. PMID:16904273

  13. Different rankings of inbred mouse strains on the Morris maze and a refined 4-arm water escape task.

    PubMed

    Wahlsten, Douglas; Cooper, Sean F; Crabbe, John C

    2005-11-30

    The submerged platform or Morris water escape task is widely used to study genetic variation in spatial learning and memory, but interpretation is sometimes difficult because of wall hugging, jumping off the platform, floating or non-spatial swim strategies. We modified the task by introducing four wide arms into the circular tank and adding features that reduced, eliminated, or compensated for several competing behaviors. Three versions of the 4-arm task were evaluated in detail, and the third version yielded good results for six of eight inbred strains. Furthermore, the 4-arm task could be scored adequately without computerized video tracking. Although performance on the 4-arm task was generally superior to the Morris maze, the extent of the improvement was strain dependent. Two strains with retinal degeneration (C3H/HeJ, FVB/NJ) performed poorly on both the Morris and 4-arm mazes, whereas C57BL/6J and DBA/2J did well on both mazes. A/J performed poorly on the Morris task but became very proficient on the 4-arm maze, despite its strong tendency to hug the walls of the tank. The BALB/cByJ strain, on the other hand, exhibited the best probe trial performance on the Morris maze but was very slow in acquiring the 4-arm task. We conclude that no single task can reveal the full richness of spatially guided behavior in a wide range of mouse genotypes. PMID:16191444

  14. Complement gene expression in hepatic and extrahepatic tissues of NZB and NZB x W (F1) mouse strains.

    PubMed Central

    Passwell, J H; Schreiner, G F; Wetsel, R A; Colten, H R

    1990-01-01

    To study the role of local production of complement proteins during the evolution of a naturally occurring immune complex disease, C3, C4, C2 and Factor B mRNA expression was assessed in several tissues of the inbred mouse strains NZB and (NZB x W) F1 hybrid. In the NZB/W F1 hybrid strain, coincident with the development of glomerulonephritis a marked increase in kidney C3 and C4 mRNA was observed; Factor B mRNA, which is expressed as a doublet in kidney and intestine, showed an increase in expression of the smaller transcript. This alteration of kidney C3, C4 and Factor B mRNA is identical to that noted in association with lupus nephritis in the MRL lpr/lpr strain and following in vivo administration of endotoxin to the BALB/c strain. The development of systemic lupus erythematosis (SLE) in the NZB/W F1 was not associated with a marked change in hepatic complement gene expression. These findings support the hypothesis that local production of complement may play a role in the pathogenesis of glomerulonephritis and other tissue injury in SLE. Images Figure 1 Figure 2 PMID:2228028

  15. Fentanyl effects on breath generation in C57BL/6J and A/J mouse strains.

    PubMed

    Fechtner, Linnea; El Ali, Mazen; Sattar, Abdus; Moore, Michael; Strohl, Kingman P

    2015-08-15

    We examined the effect of fentanyl on chemoresponsiveness in mouse strains divergent in the expression of spontaneous and post-hypoxic pauses. Frequency and tidal volume were recorded with plethysmography in A/J and C57BL/6J (B6) male mice. Mice selected at random received an intraperitoneal (IP) injection of either saline, low dose fentanyl (LDF = 0.04 mg/kg), or high dose fentanyl (HDF = 0.4 mg/kg) under hypoxia (8% O2) or hyperoxia (100%O2). LDF produced a decrease in frequency during hypoxia in B6, but not A/J, mice. HDF significantly decreased frequency and tidal volume in both strains under hypoxia and hyperoxia (p<0.01); naloxone, an opioid antagonist, reversed this response. The acute administration of fentanyl at any dose did not promote apneas in strains of mice exhibiting regular or irregular respiratory patterns. However, higher doses depressed respiratory frequency in both strains. The B6 mice responded with a depressive response to hypoxia that did not recover with reoxygenation, but did recover with time or naloxone. PMID:25936679

  16. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    PubMed

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes. PMID:26923756

  17. A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors.

    PubMed

    Heger, Klaus; Kober, Maike; Rieß, David; Drees, Christoph; de Vries, Ingrid; Bertossi, Arianna; Roers, Axel; Sixt, Michael; Schmidt-Supprian, Marc

    2015-06-01

    Replication-deficient recombinant adenoviruses are potent vectors for the efficient transient expression of exogenous genes in resting immune cells. However, most leukocytes are refractory to efficient adenoviral transduction as they lack expression of the coxsackie/adenovirus receptor (CAR). To circumvent this obstacle, we generated the R26/CAG-CARΔ1(StopF) (where R26 is ROSA26 and CAG is CMV early enhancer/chicken β actin promoter) knock-in mouse line. This strain allows monitoring of in situ Cre recombinase activity through expression of CARΔ1. Simultaneously, CARΔ1 expression permits selective and highly efficient adenoviral transduction of immune cell populations, such as mast cells or T cells, directly ex vivo in bulk cultures without prior cell purification or activation. Furthermore, we show that CARΔ1 expression dramatically improves adenoviral infection of in vitro differentiated conventional and plasmacytoid dendritic cells (DCs), basophils, mast cells, as well as Hoxb8-immortalized hematopoietic progenitor cells. This novel dual function mouse strain will hence be a valuable tool to rapidly dissect the function of specific genes in leukocyte physiology. PMID:25787118

  18. Brucella pinnipedialis hooded seal (Cystophora cristata) strain in the mouse model with concurrent exposure to PCB 153.

    PubMed

    Nymo, Ingebjørg H; das Neves, Carlos G; Tryland, Morten; Bårdsen, Bård-Jørgen; Santos, Renato Lima; Turchetti, Andreia Pereira; Janczak, Andrew M; Djønne, Berit; Lie, Elisabeth; Berg, Vidar; Godfroid, Jacques

    2014-05-01

    Brucellosis, a worldwide zoonosis, is linked to reproductive problems in primary hosts. A high proportion of Brucella-positive hooded seals (Cystophora cristata) have been detected in the declined Northeast Atlantic stock. High concentrations of polychlorinated biphenyls (PCBs) have also been discovered in top predators in the Arctic, including the hooded seal, PCB 153 being most abundant. The aim of this study was to assess the pathogenicity of Brucella pinnipedialis hooded seal strain in the mouse model and to evaluate the outcome of Brucella spp. infection after exposure of mice to PCB 153. BALB/c mice were infected with B. pinnipedialis hooded seal strain or Brucella suis 1330, and half from each group was exposed to PCB 153 through the diet. B. pinnipedialis showed a reduced pathogenicity in the mouse model as compared to B. suis 1330. Exposure to PCB 153 affected neither the immunological parameters, nor the outcome of the infection. Altogether this indicates that it is unlikely that B. pinnipedialis contribute to the decline of hooded seals in the Northeast Atlantic. PMID:24534631

  19. Expression analysis of mouse Rhobtb3 using a LacZ reporter and preliminary characterization of a knockout strain.

    PubMed

    Lutz, Julia; Grimm-Günter, Eva-Maria S; Joshi, Pooja; Rivero, Francisco

    2014-11-01

    RhoBTB3 is an atypical member of the Rho family of small GTPases. It localizes at the Golgi apparatus and endosomes and is involved in vesicle trafficking and in targeting proteins for degradation in the proteasome. Previous studies using Northern blot analysis showed that Rhobtb3 is ubiquitously expressed in adult mice, but expression is particularly high in brain, heart and uterus. The gene is also expressed between embryonic days 11.5 and 17.5. To investigate the specific cell types that express this gene across tissues, both in the embryo and in the adult organism, we have made use of a gene trap mouse strain that expresses the LacZ gene under the transcriptional control of the endogenous Rhobtb3 promoter. Histochemical detection of β-galactosidase expression revealed a profile characterized by nearly ubiquitous expression of Rhobtb3 in the embryo, but with particularly high levels in bone, cartilage, all types of muscle, testis and restricted areas of the nervous system. In the adult, expression persists at much lower levels in cardiac muscle, the tunica media of blood vessels and cartilage and at high levels in the seminiferous tubules. A general preliminary characterization of this gene trap mouse strain revealed reduced viability, a postnatal growth defect and reduced testis size. Our results should pave the way for future studies aimed at investigating the roles of RhoBTB3 in tissue development and in cardiac, vascular and testicular function. PMID:24923387

  20. Body Composition QTLs Identified in Intercross Populations Are Reproducible in Consomic Mouse Strains

    PubMed Central

    Lin, Cailu; Fesi, Brad D.; Marquis, Michael; Bosak, Natalia P.; Theodorides, Maria L.; Avigdor, Mauricio; McDaniel, Amanda H.; Duke, Fujiko F.; Lysenko, Anna; Khoshnevisan, Amin; Gantick, Brian R.; Arayata, Charles J.; Nelson, Theodore M.; Bachmanov, Alexander A.; Reed, Danielle R.

    2015-01-01

    Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL. PMID:26551037

  1. Hidden in plain sight: spike-wave discharges in mouse inbred strains.

    PubMed

    Letts, V A; Beyer, B J; Frankel, W N

    2014-07-01

    Twenty-seven inbred strains of mice were tested for spike-wave discharge (SWD) activity by video-electroencephalographic recordings over a 24-h recording period. Eight strains had reproducible, frequent SWDs, including five strains (C57BLKS/J, CBA/J, DBA/1J, NOR/LtJ, SM/J) previously undiagnosed for this distinctive phenotype. Eighteen other strains exhibited no such activity. Spike-wave discharges usually occurred while the subject was motionless, and in a significant number of annotated instances coincided with an arrest of the subject's relatively unrestrained locomotor activity, which resumed immediately after the discharge ended. In all five new strains, SWDs were suppressed by ethosuximide administration. From the genealogy of inbred strains, we suggest that two ancestors, A and DBA, transmitted genotypes required for SWD in all positive strains. Together these strains with SWDs provide new opportunities to understand the genetic core susceptibility of this distinctive electroencephalographic activity and to explore its relationship to absence epilepsy, a human disorder for which few genes are known. PMID:24861780

  2. Global gene expression profiling reveals similarities and differences among mouse pluripotent stem cells of different origins and strains

    PubMed Central

    Sharova, Lioudmila V.; Sharov, Alexei A.; Piao, Yulan; Shaik, Nabeebi; Sullivan, Terry; Stewart, Colin L.; Hogan, Brigid L.M.; Ko, Minoru S.H.

    2007-01-01

    Pluripotent stem cell lines with similar phenotypes can be derived from both blastocysts (embryonic stem cells, ESC) and primordial germ cells (embryonic germ cells, EGC). Here, we present a compendium DNA microarray analysis of multiple mouse ESCs and EGCs from different genetic backgrounds (strains 129 and C57BL/6) cultured under standard conditions and in differentiation-promoting conditions by the withdrawal of Leukemia Inhibitory Factor (LIF) or treatment with retinoic acid (RA). All pluripotent cell lines showed similar gene expression patterns, which separated them clearly from other tissue stem cells with lower developmental potency. Differences between pluripotent lines derived from different sources (ESC vs. EGC) were smaller than differences between lines derived from different mouse strains (129 vs. C57BL/6). Even in the differentiation-promoting conditions, these pluripotent cells showed the same general trends of gene expression changes regardless of their origin and genetic background. These data indicate that ESCs and EGCs are indistinguishable based on global gene expression patterns alone. On the other hand, a detailed comparison between a group of ESC lines and a group of EGC lines identified 20 signature genes whose average expression levels were consistently higher in ESC lines, and 84 signature genes whose average expression levels were consistently higher in EGC lines, irrespective of mouse strains. Similar analysis identified 250 signature genes whose average expression levels were consistently higher in a group of 129 cell lines, and 337 signature genes whose average expression levels were consistently higher in a group of C57BL/6 cell lines. Although none of the genes was exclusively expressed in either ESCs versus EGCs or 129 versus C57BL/6, in combination these signature genes provide a reliable separation and identification of each cell type. Differentiation-promoting conditions also revealed some minor differences between the cell

  3. Forty mouse strain survey of voluntary calcium intake, blood calcium, and bone mineral content.

    PubMed

    Tordoff, Michael G; Bachmanov, Alexander A; Reed, Danielle R

    2007-08-15

    We measured voluntary calcium intake, blood calcium, and bone mineral content of male and female mice from 40 inbred strains. Calcium intakes were assessed using 48-h two-bottle tests with a choice between water and one of the following: water, 7.5, 25, and 75 mM CaCl(2), then 7.5, 25, and 75 mM calcium lactate (CaLa). Intakes were affected by strain, sex, anion, and concentration. In 11 strains females consumed more calcium than did males and in the remaining 29 strains there were no sex differences. Nine strains drank more CaLa than CaCl(2) whereas only one strain (JF1/Ms) drank more CaCl(2) than CaLa. Some strains had consistently high calcium intakes and preferred all calcium solutions relative to water (e.g., PWK/PhJ, BTBR T(+)tf/J, JF1/Ms). Others had consistently low calcium intakes and avoided all calcium solutions relative to water (e.g., KK/H1J, C57BL/10J, CE/J, C58/J). After behavioral tests, blood was sampled and assayed for pH, ionized calcium concentration, and plasma total calcium concentration. Bone mineral density and content were assessed by DEXA. There were no significant correlations between any of these physiological measures and calcium intake. However, strains of mice that had the highest calcium intakes generally fell at the extremes of the physiological distributions. We conclude that the avidity for calcium is determined by different genetic architecture and thus different physiological mechanisms in different strains. PMID:17493644

  4. Forty mouse strain survey of voluntary calcium intake, blood calcium, and bone mineral content

    PubMed Central

    Tordoff, Michael G.; Bachmanov, Alexander A.; Reed, Danielle R.

    2007-01-01

    We measured voluntary calcium intake, blood calcium, and bone mineral content of male and female mice from 40 inbred strains. Calcium intakes were assessed using 48-h two-bottle tests with a choice between water and one of the following: water, 7.5, 25, and 75 mM CaCl2, then 7.5, 25, and 75 mM calcium lactate (CaLa). Intakes were affected by strain, sex, anion, and concentration. In 11 strains females consumed more calcium than did males and in the remaining 29 strains there were no sex differences. Nine strains drank more CaLa than CaCl2 whereas only one strain (JF1/Ms) drank more CaCl2 than CaLa. Some strains had consistently high calcium intakes and preferred all calcium solutions relative to water (e.g., PWK/PhJ, BTBR T+tf/J, JF1/Ms). Others had consistently low calcium intakes and avoided all calcium solutions relative to water (e.g., KK/H1J, C57BL/10J, CE/J, C58/J). After behavioral tests, blood was sampled and assayed for pH, ionized calcium concentration, and plasma total calcium concentration. Bone mineral density and content were assessed by DEXA. There were no significant correlations between any of these physiological measures and calcium intake. However, strains of mice that had the highest calcium intakes generally fell at the extremes of the physiological distributions. We conclude that the avidity for calcium is determined by different genetic architecture and thus different physiological mechanisms in different strains. PMID:17493644

  5. What makes a good mother? Implication of inter-, and intrastrain strain "cross fostering" for emotional changes in mouse offspring.

    PubMed

    Lerch, Sandra; Brandwein, Christiane; Dormann, Christof; Gass, Peter; Chourbaji, Sabine

    2014-11-01

    Currently, the mouse represents the preferred model organism among mammals used for animal studies. Due to a great availability of mutant strains it represents a standard method to analyze in vivo the effects of targeted gene manipulations. While this - at least in theory - represents a valuable tool to elucidate the pathophysiology of certain human diseases, there are several caveats which need to be considered working with animals. In our study we aimed at elucidating, how a widely established breeding strategy, i.e. the use of "foster mothers" to save the survival of compromised mouse pups for ongoing experiments, per se, affects the emotional phenotype of the fostered offspring. Since it is a popular method to use outbred strains like NMRI to do this job, we sought to evaluate the potential effects of such an artificial postnatal condition and compare either offspring nurtured by their biological mothers or two different strains of foster mothers. Hence we analysed changes in maternal care and later on the emotional behaviour of male and female C57BL/6 mice reared by (i) their biological C57BL/6 mothers, (ii) C57BL/6 foster mothers and (iii) NMRI foster mothers in a behavioural test battery. In addition we assessed corticosterone levels as indicator for stress-physiological changes. Besides clear differences in maternal behaviour, our study indicates an altered emotional state (i.e. differences in anxiety and depressive-like features) in mice reared by different "categories" of mothers, which emphasizes the importance to embed such perinatal conditions in the evaluation of animal-deriving data. PMID:25151929

  6. Susceptibility of Different Mouse Wild Type Strains to Develop Diet-Induced NAFLD/AFLD-Associated Liver Disease

    PubMed Central

    Fengler, Vera H. I.; Macheiner, Tanja; Kessler, Sonja M.; Czepukojc, Beate; Gemperlein, Katja; Müller, Rolf; Kiemer, Alexandra K.; Magnes, Christoph; Haybaeck, Johannes; Lackner, Carolin; Sargsyan, Karine

    2016-01-01

    Although non-alcoholic and alcoholic fatty liver disease have been intensively studied, concerning pathophysiological mechanisms are still incompletely understood. This may be due to the use of different animal models and resulting model-associated variation. Therefore, this study aimed to compare three frequently used wild type mouse strains in their susceptibility to develop diet-induced features of non-alcoholic/alcoholic fatty liver disease. Fatty liver disease associated clinical, biochemical, and histological features in C57BL/6, CD-1, and 129Sv WT mice were induced by (i) high-fat diet feeding, (ii) ethanol feeding only, and (iii) the combination of high-fat diet and ethanol feeding. Hepatic and subcutaneous adipose lipid profiles were compared in CD-1 and 129Sv mice. Additionally hepatic fatty acid composition was determined in 129Sv mice. In C57BL/6 mice dietary regimens resulted in heterogeneous hepatic responses, ranging from pronounced steatosis and inflammation to a lack of any features of fatty liver disease. Liver-related serum biochemistry showed high deviations within the regimen groups. CD-1 mice did not exhibit significant changes in metabolic and liver markers and developed no significant steatosis or inflammation as a response to dietary regimens. Although 129Sv mice showed no weight gain, this strain achieved most consistent features of fatty liver disease, apparent from concentration alterations of liver-related serum biochemistry as well as moderate steatosis and inflammation as a result of all dietary regimens. Furthermore, the hepatic lipid profile as well as the fatty acid composition of 129Sv mice were considerably altered, upon feeding the different dietary regimens. Accordingly, diet-induced non-alcoholic/alcoholic fatty liver disease is most consistently promoted in 129Sv mice compared to C57BL/6 and CD-1 mice. As a conclusion, this study demonstrates the importance of genetic background of used mouse strains for modeling diet

  7. The Postnatal Development of d-Serine in the Retinas of Two Mouse Strains, Including a Mutant Mouse with a Deficiency in d-Amino Acid Oxidase and a Serine Racemase Knockout Mouse

    PubMed Central

    2015-01-01

    d-Serine, an N-methyl d-aspartate receptor coagonist, and its regulatory enzymes, d-amino acid oxidase (DAO; degradation) and serine racemase (SR; synthesis), have been implicated in crucial roles of the developing central nervous system, yet the functional position that they play in regulating the availability of d-serine throughout development of the mammalian retina is not well-known. Using capillary electrophoresis and a sensitive method of enantiomeric amino acid separation, we were able to determine total levels of d-serine at specific ages during postnatal development of the mouse retina in two different strains of mice, one of which contained a loss-of-function point mutation for DAO while the other was a SR knockout line. Each mouse line was tested against conspecific wild type (WT) mice for each genetic strain. The universal trend in all WT and transgenic mice was a large amount of total retinal d-serine at postnatal age 2 (P2), followed by a dramatic decrease as the mice matured into adulthood (P70–80). SR knockout mice retinas had 41% less d-serine than WT retinas at P2, and 10 times less as an adult. DAO mutant mice retinas had significantly elevated levels of d-serine when compared to WT retinas at P2 (217%), P4 (223%), P8 (194%), and adulthood (227%). PMID:25083578

  8. COMPARISON OF SYSTEMIC AND MUCOSAL ROUTES OF SENSITIZATION TO OVALBUMIN ANTIGEN IN THREE MOUSE STRAINS

    EPA Science Inventory

    Several studies have shown strain differences in allergic lung responses following ovalbumin (OVA) antigen sensitization and challenge. The purpose of this study was to determine whether these differences were maintained between systemic and mucosal sensitization routes, and to ...

  9. Aeromonas Caviae Strain Induces Th1 Cytokine Response in Mouse Intestinal Tract

    EPA Science Inventory

    Aeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus. Microarray profiling of murine small i...

  10. Resistance of novel mouse strains different in MHC class I and the NKC domain to the development of experimental tumors.

    PubMed

    Fišerová, Anna; Richter, Jan; Čapková, Katarína; Bieblová, Jana; Mikyšková, Romana; Reiniš, Milan; Indrová, Marie

    2016-08-01

    To elucidate the immunological mechanisms critical for tumor progression, we bred novel mouse strains, different in the NKC and H-2D domains. We used inbreeding to generate hybrids of Balb/c and C57BL/6 of stable H-2Db+d-NK1.1neg and H-2Db-d+NK1.1high phenotypes. We analyzed the growth of three established MHC class I-deficient tumor cell lines: TC-1/A9 tumor (HPV-associated) and B16F10 melanoma, both syngeneic to C57BL/6, and the MCB8 (3-methycholanthrene-induced tumor) syngeneic to Balb/c. Furthermore, we induced colorectal carcinoma by azoxymethane-DSS treatment to test the susceptibility to chemically-induced primary cancer. We found that the novel strains spontaneously regressed the tumor transplants syngeneic to both Balb/c (MCB8) and C57BL/6 (B16F10 and TC-1/A9) mice. The H2-Db+d-NK1.1neg, but not the H2-Db-d+NK1.1high strain was also highly resistant to chemically-induced colorectal cancer in comparison to the parental mice. The immune changes during TC-1/A9 cancer development involved an increase of the NK cell distribution in the peripheral blood and spleen along with higher expression of NKG2D activation antigen; this was in correlation with the time-dependent rise of cytotoxic activity in comparison to C57BL/6 mice. The TC-1/A9 cancer regression was accompanied by higher proportion of B cells in the spleen and B220+/CD86+ activated antigen-presenting B cells distributed in the lymphoid organs, as well as in the periphery. The changes in the T-cell population were represented mainly by the prevalence of T helper cells reflected by grown CD4/CD8 ratio, most prominent in the b+d-NK1.1neg strain. The results of the present study imply usefulness of the two novel mouse strains as an experimental model for further studies of tumor resistance mechanisms. PMID:27279019

  11. Safety, efficacy and efficiency of laser-assisted IVF in subfertile mutant mouse strains

    PubMed Central

    Li, Ming-Wen; Kinchen, Kristy L; Vallelunga, Jadine M; Young, Diana L; Wright, Kaleb D K; Gorano, Lisa N; Wasson, Katherine; Lloyd, K C Kent

    2013-01-01

    In the present report we studied the safety, efficacy and efficiency of using an infrared laser to facilitate IVF by assessing fertilization, development and birth rates after laser-zona drilling (LZD) in 30 subfertile genetically modified (GM) mouse lines. We determined that LZD increased the fertilization rate four to ten times that of regular IVF, thus facilitating the derivation of 26 of 30 (86.7%) GM mouse lines. Cryopreserved two-cell stage embryos derived by LZD-assisted IVF were recovered and developed to blastocysts in vitro at the same rate as frozen–thawed embryos derived by regular IVF. Surprisingly after surgical transfer to pseudopregnant recipients the birth rate of embryos derived by LZD-assisted IVF was significantly lower than that of embryos derived by regular IVF. However this result could be completely mitigated by the addition of 0.25 M sucrose to the culture medium during LZD which caused the oocyte to shrink in volume relative to the perivitelline space. By increasing the distance from the laser target site on the zona pellucida, we hypothesize that the hyperosmotic effect of sucrose reduced the potential for laser-induced cytotoxic thermal damage to the underlying oocytes. With appropriate preparation and cautious application, our results indicate that LZD-assisted IVF is a safe, efficacious and efficient assisted reproductive technology for deriving mutant mouse lines with male factor infertility and subfertility caused by sperm–zona penetration defects. PMID:23315689

  12. Friend strain of spleen focus-forming virus: a recombinant between mouse type C ecotropic viral sequences and sequences related to xenotropic virus.

    PubMed Central

    Troxler, D H; Boyars, J K; Parks, W P; Scolnick, E M

    1977-01-01

    The genome of the Friend strain of the spleen focus-forming virus (SFFV) has been analyzed by molecular hybridization. SFFV is composed of genetic sequences homologous to Friend type C helper virus (F-MuLV) and SFFV-specific sequences not present in F-MuLV. These SFFV-specific sequences are present in both the Friend and Rauscher strains of murine erythroleukemia virus. The SFFV-specific sequences are partially homologous to three separate strains of mouse xenotropic virus but not to several cloned mouse ecotropic viruses. Thus, the Friend strain of SFFV appears to be a recombinant between a portion of the F-MuLV genome and RNA sequences that are highly related to murine xenotropic viruses. The implications of the acquisition of the xenotropic virus-related sequences are discussed in relation to the leukemogenicity of SFFV, and a model for the pathogenicity of other murine leukemia-inducing viruses is proposed. PMID:194058

  13. Genetics of body weight in the LXS recombinant inbred mouse strains

    SciTech Connect

    Bennett, Beth; Carosone-Line, Phyllis; Lu, Lu; Chesler, Elissa J; Johnson, Thomas

    2005-01-01

    This is the first phenotypic analysis of 75 new recombinant inbred (RI) strains derived from ILS and ISS progenitors. We analyzed body weight in two independent cohorts of female mice at various ages and in males at 60 days. Body weight is a complex trait which has been mapped in numerous crosses in rodents. The LXS RI strains displayed a large range of weights, transgressing those of the inbred progenitors, supporting the utility of this large panel for mapping traits not selected in the progenitors. Numerous QTLs for body weight mapped in singleand multilocus scans. We assessed replication between these and previously reported QTLs based on overlapping confidence intervals of published QTLs for body weight at 60 days and used meta-analyses to determine combined p values for three QTL regions located on Chromosomes 4, 5, and 11. Strain distribution patterns of microsatellite marker genotypes, weight, and other phenotypes are available on Web- QTL (http://www.webqtl.org/search.html) and allow genetic mapping of any heritable quantitative phenotype measured in these strains. We report one such analysis, correlating brain and body weights. Large reference panels of RI strains, such as the LXS, are invaluable for identifying genetic correlations, GXE (Gene X Environment) interactions, and replicating previously identified QTLs.

  14. Transmural Myocardial Strain in Mouse: Quantification of High-Resolution MR Tagging using HARP Analysis

    PubMed Central

    Zhong, Jia; Liu, Wei; Yu, Xin

    2009-01-01

    MR tagging allows noninvasive examination of regional myocardial function with high accuracy and reproducibility. Current tagging method is limited by low tagging resolution for accurate transmural strain quantification. Previously, a SPAMM-based method was proposed to increase the tagging resolution by combining two or more tagged images with different tagging grid positions. However, there has been limited application due to the challenge in image processing of multiple data sets. In the current study, we propose a HARP-based method for automated and fast analysis of high-resolution tagged images. First-order harmonic peaks from low tagging resolution images were combined to generate the composite second-order harmonic peak for strain computation. The combined images reached a tagging resolution of 0.3 mm. The proposed method was applied to the quantification of transmural myocardial wall strain in 7 normal C57BL/6 mice. Principal strains, as well as radial and circumferential strains, were quantified using the current method. PMID:19319888

  15. Genetic Divergence in Mandible Form in Relation to Molecular Divergence in Inbred Mouse Strains

    PubMed Central

    Atchley, W. R.; Newman, S.; Cowley, D. E.

    1988-01-01

    Genetic divergence in the form of the mandible is examined in ten inbred strains of mice. Several univariate and multivariate genetic distance estimates are given for the morphological data and these estimates are compared to measures of genealogical and molecular divergence. Highly significant divergence occurs among the ten strains in all 11 mandible traits considered individually and simultaneously. Genealogical relationship among strains is highly correlated with genetic divergence in single locus molecular traits. However, the concordance between genealogical relationship and multivariate genetic divergence in morphology is much more complex. Whether there is a significant correlation between morphological divergence and genealogy depends upon the method of analysis and the particular genetic distance statistic being employed. PMID:3220250

  16. Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract

    SciTech Connect

    Hayes, S L; Lye, D J; McKinstry, Craig A.; Vesper, Sephen J.

    2010-01-01

    Aeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus. Microarray profiling of murine small intestinal extracts, 24 hours after oral infection with an A. caviae strain, provides evidence of a Th1 type immune response. A large number of gamma-interferon (γ-IFN) induced genes are up-regulated as well as several tumor necrosis factor-alpha (TNF-α) transcripts. A. caviae has always been considered as opportunistic pathogen because it lacks obvious virulence factors. This current effort suggests that an A. caviae strain can colonize the murine intestinal tract and cause what has been described by others as a dysregulatory cytokine response. This response could explain why a number of diarrheal waterborne disease cases have been attributed to A. caviae even though it lacks obvious enteropathogenic properties.

  17. Double replacement gene targeting for the production of a series of mouse strains with different prion protein gene alterations

    SciTech Connect

    Moore, R.C.; Redhead, N.J.; Selfridge, J.

    1995-09-01

    We have developed a double replacement gene targeting strategy which enables the production of a series of mouse strains bearing different subtle alterations to endogenous genes. This is a two-step process in which a region of the gene of interest is first replaced with a selectable marker to produce an inactivated allele, which is then re-targeted with a second vector to reconstruct the inactivated allele, concomitantly introducing an engineered mutation. Five independent embryonic stem cell lines have been produced bearing different targeted alterations to the prion protein gene, including one which raises the level of expression. We have constructed mice bearing the codon 101 proline to leucine substitution linked to the human familial prion disease, Gerstmann-Straussler-Scheinker syndrome. We anticipate that this procedure will have applications to the study of human inherited diseases and the development of therapies. 43 refs., 6 figs., 1 tab.

  18. Effects of Malignant Effusions on the Mitotic Index of L Strain Mouse Cells Grown in Tissue Culture

    PubMed Central

    Hrushovetz, S. B.; Ewaniuk, Meriam H.

    1963-01-01

    By employing a clone of L strain mouse fibroblasts (LE) which does not exhibit cell clumping and lysis (cytolytic antibody reaction), it was possible to screen for the presence of growth-regulating factors in human sera and effusions, exclusive of an antigen-antibody reaction. Under conditions of the test a mitotic index greater than 20% indicated the presence of a growth-promoting factor. A total of 11 pleural effusions was tested. Four of the eight malignant effusions possessed a growth-promoting factor, while none of the three non-malignant effusions or the one sample of human umbilical cord serum possessed such a factor. Overnight storage of the unfiltered effusions at 5° C. resulted in complete loss of the growthpromoting activity. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:14052976

  19. Organ-Specific Protective Role of NKT Cells in Virus-Induced Inflammatory Demyelination and Myocarditis Depends on Mouse Strain

    PubMed Central

    Kawai, Eiichiro; Sato, Fumitaka; Omura, Seiichi; Martinez, Nicholas E.; Reddy, Pratap C.; Taniguchi, Masaru; Tsunoda, Ikuo

    2014-01-01

    Theiler’s murine encephalomyelitis virus (TMEV) can induce demyelination or myocarditis in susceptible mouse strains. A deficiency of NKT cells exacerbated TMEV-induced demyelinating disease (TMEV-IDD) in SJL/J and BALB/c mice. In C57BL/6 background, however, NKT-cell-deficient Jαt 18 KO mice remained as resistant to TMEV-IDD as wild-type mice. Echocardiography and histology showed that Jα18 KO mice developed more severe myocarditis (greater T cell infiltration and fibrosis) than wild-type mice, suggesting a protective role of NKT cells in myocarditis in C57BL/6 mice. Jα18 KO mice had higher cardiac viral RNA and anti-viral antibody titers, but had lower lymphoproliferation and IL-4 and IL-10 production. PMID:25434008

  20. Experimental Hamster Infection with a Strain of Leptospira borgpetersenii Ballum Isolated from a Reservoir Mouse in New Caledonia

    PubMed Central

    Matsui, Mariko; Roche, Louise; Soupé-Gilbert, Marie-Estelle; Roudier, Martine; Moniquet, Vincent; Goarant, Cyrille

    2015-01-01

    Leptospirosis is a neglected zoonosis caused by pathogenic Leptospira. In this study, we characterized the virulence of isolate B3-13S obtained from a wild mouse (Mus musculus) captured in New Caledonia, subsequently identified as a bacterium belonging to the L. borgpetersenii serogroup Ballum. Hamsters were infected with an intraperitoneal injection of 2 × 108 bacteria, resulting in severe histopathological organ damages consistent with tissue lesions previously observed with other strains. Hamsters were also injected with 1 × 108 or 5 × 107 bacteria and animals that recovered showed renal carriage of leptospires in concentrations similar to the bacterial load quantified in mouse kidneys, with urinary shedding of bacteria up to 4 weeks postinfection. The serogroup Ballum is increasingly reported in human leptospirosis, and these results highlight the use of the B3-13S isolate for the development of models resulting in either severe acute or chronic forms of the infection, allowing for better characterization of its pathogenesis. PMID:25758655

  1. Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract

    EPA Science Inventory

    Aeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus,. Microarray profiling of...

  2. Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades.

    PubMed

    Wahlsten, Douglas; Bachmanov, Alexander; Finn, Deborah A; Crabbe, John C

    2006-10-31

    If we conduct the same experiment in two laboratories or repeat a classical study many years later, will we obtain the same results? Recent research with mice in neural and behavioral genetics yielded different results in different laboratories for certain phenotypes, and these findings suggested to some researchers that behavior may be too unstable for fine-scale genetic analysis. Here we expand the range of data on this question to additional laboratories and phenotypes, and, for the first time in this field, we formally compare recent data with experiments conducted 30-50 years ago. For ethanol preference and locomotor activity, strain differences have been highly stable over a period of 40-50 years, and most strain correlations are in the range of r = 0.85-0.98, as high as or higher than for brain weight. For anxiety-related behavior on the elevated plus maze, on the other hand, strain means often differ dramatically across laboratories or even when the same laboratory is moved to another site within a university. When a wide range of phenotypes is considered, no inbred strain appears to be exceptionally stable or labile across laboratories in any general sense, and there is no tendency to observe higher correlations among studies done more recently. Phenotypic drift over decades for most of the behaviors examined appears to be minimal. PMID:17053075

  3. Stable Listeria monocytogenes live vaccine candidate strains with graded attenuation on the mouse model.

    PubMed

    Linde, K; Abraham, A A; Beer, J

    1991-02-01

    Metabolic drift (antibiotics resistance) mutations were used to construct stable two (and three) marker vaccine candidate strains of the predominant Listeria monocytogenes serotypes 1/2a and 4b by stepwise selection. Derived from wild-type strains, spontaneous chromosomal streptomycin-resistant clones with their i.p. LD50 elevated from less than or equal to 10(5.0) c.f.u. to approximately 10(6.1) c.f.u. were used in the second step to isolate the rifampicin-resistant mutants with i.p. LD50 values ranging from 10(6.6) to 10(7.4). On i.p. immunization with fully tolerated doses (less than or equal to 1% LD50), these potential vaccine strains were found to protect not less than 95% of the mice against a lethal (approximately 100 LD50) challenge with the homologous wild-type strain. Further elevation of the i.p. LD50 to greater than 10(8.3) c.f.u. by means of a third attenuating fosfomycin-resistance marker resulted in overattenuation and reduced protective capacity. PMID:1905446

  4. The effect of handling method on the mouse grimace scale in two strains of laboratory mice

    PubMed Central

    Leach, Matthew C

    2015-01-01

    Pain assessment in laboratory animals is an ethical and legal requirement. The mouse grimace scale (MGS) is a new method of pain assessment deemed to be both accurate and reliable, and observers can be rapidly trained to use it. In order for a new pain assessment technique to be effective, we must ensure that the score awarded by the technique is only influenced by pain and not by other husbandry or non-painful but integral aspects of research protocols. Here, we studied 16 male mice, housed under standard laboratory conditions. Eight mice were randomly assigned to tail handling and eight to tube handling on arrival at the unit. On each occasion the mice were removed from their cage for routine husbandry, they were picked up using their assigned handling method. Photographs of the mouse faces were then scored by treatment-blind observers as per the MGS manual (see Nature Methods 2010, Vol. 7, pp 447–449), and scores from the two groups were compared. There was no significant difference in MGS scores between the mice that had been handled using a tube compared with the tail. Consequently, these methods of handling did not influence the baseline grimace score given, suggesting that these handling techniques are not confounding factors when establishing baseline MGS scores, further validating this technique. PMID:26657061

  5. OZONE INDUCED HEMATOLOGICAL CHANGES IN MOUSE STRAINS WITH DIFFERENTIAL LEVELS OF ERYTHROCYTE G-6-PD ACTIVITY AND VITAMIN E STATUS (JOURNAL VERSION)

    EPA Science Inventory

    A single short term in vivo exposure (6 hr) to O3 (i.e., 0.3, 0.9, 1.5 ppm) markedly affected several hematological parameters in males of two mouse strains (C57L/J and A/J) reared on either a vitamin E normal or deficient diet. Of particular significance is that at the lowest co...

  6. A new atypical genotype mouse virulent strain of Toxoplasma gondii isolated from the heart of a wild caught puma (Felis concolor) from Durango, Mexico

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nothing is known of the genetic diversity of Toxoplasma gondii circulating in wildlife in Mexico. In the present study, a mouse virulent T. gondii strain was isolated from the heart of a wild puma (Felis concolor). The puma was found roaming in outskirt of Durango City, Mexico and tranquailized for ...

  7. Differences in Mucosal Gene Expression in the Colon of Two Inbred Mouse Strains after Colonization with Commensal Gut Bacteria

    PubMed Central

    Blaut, Michael; Loh, Gunnar

    2013-01-01

    The host genotype has been proposed to contribute to individually composed bacterial communities in the gut. To provide deeper insight into interactions between gut bacteria and host, we associated germ-free C3H and C57BL/10 mice with intestinal bacteria from a C57BL/10 donor mouse. Analysis of microbiota similarity between the animals with denaturing gradient gel electrophoresis revealed the development of a mouse strain-specific microbiota. Microarray-based gene expression analysis in the colonic mucosa identified 202 genes whose expression differed significantly by a factor of more than 2. Application of bioinformatics tools demonstrated that functional terms including signaling/secretion, lipid degradation/catabolism, guanine nucleotide/guanylate binding and immune response were significantly enriched in differentially expressed genes. We had a closer look at the 56 genes with expression differences of more than 4 and observed a higher expression in C57BL/10 mice of the genes coding for Tlr1 and Ang4 which are involved in the recognition and response to gut bacteria. A higher expression of Pla2g2a was detected in C3H mice. In addition, a number of interferon-inducible genes were higher expressed in C3H than in C57BL/10 mice including Gbp1, Mal, Oasl2, Ifi202b, Rtp4, Ly6g6c, Ifi27l2a, Usp18, Ifit1, Ifi44, and Ly6g indicating that interferons may play an essential role in microbiota regulation. However, genes coding for interferons, their receptors, factors involved in interferon expression regulation or signaling pathways were not differentially expressed between the two mouse strains. Taken together, our study confirms that the host genotype is involved in the establishment of host-specific bacterial communities in the gut. Based on expression differences after colonization with the same bacterial inoculum, we propose that Pla2g2a and interferon-dependent genes may contribute to this phenomenon. PMID:23951309

  8. Mouse strains for the ubiquitous or conditional overexpression of the Flii gene.

    PubMed

    Thomsen, Nicole; Chappell, Anna; Ali, Radiya G; Jones, Tamsin; Adams, Damian H; Matthaei, Klaus I; Campbell, Hugh D; Cowin, Allison J; Arkell, Ruth M

    2011-08-01

    The gelsolin related actin binding protein, Flii, is able to regulate wound healing; mice with decreased Flii expression show improved wound healing whereas mice with elevated Flii expression exhibit impaired wound healing. In both mice and humans Flii expression increases with age and amelioration of FLII activity represents a possible therapeutic strategy for improved wound healing in humans. Despite analysis of Flii function in a variety of organisms we know little of the molecular mechanisms underlying Flii action. Two new murine alleles of Flii have been produced to drive constitutive or tissue-specific expression of Flii. Each strain is able to rescue the embryonic lethality associated with a Flii null allele and to impair wound healing. These strains provide valuable resources for ongoing investigation of Flii function in a variety of biological processes. PMID:21786402

  9. Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth.

    PubMed Central

    Fallon, M T; Benjamin, W H; Schoeb, T R; Briles, D E

    1991-01-01

    We have previously shown that intranasal infection of mice with mouse hepatitis virus (MHV) strain UAB (MHV-UAB) increases their resistance to Salmonella typhimurium injected intravenously 6 days later. To study how salmonella resistance was induced, BALB/cAnNCr mice were infected with salmonella strains carrying specific genetic alterations. One set of studies compared the effect of MHV infection on subsequent salmonella infections with AroA- (avirulent) and Aro+ (virulent) salmonellae. Unlike its effect on Aro+ salmonellae, MHV failed to reduce the number of AroA- salmonellae recovered from mice. Because AroA- S. typhimurium shows almost no growth in vivo, this failure indicated that the effect of MHV on salmonella resistance required growth of the infecting salmonellae. In other studies, the effect of MHV infection on both growth and killing were monitored simultaneously in mice with growing salmonellae carrying a single copy of the temperature-sensitive pHSG422 plasmid, which is unable to replicate in vivo. MHV infection reduced salmonella growth but caused no increase in salmonella killing. MHV infection of mice given wild-type salmonellae also resulted in no increase in salmonella killing 4 h after salmonella challenge. These studies demonstrate that MHV-UAB infection increases host resistance to salmonellae by enhancing suppression of bacterial growth instead of by increasing the amount of salmonella killing. PMID:1847697

  10. Age, Strain, and Gender as Factors for Increased Sensitivity of the Mouse Lung to Inhaled Ozone

    PubMed Central

    Vancza, Elizabeth M.; Galdanes, Karen; Gunnison, Al; Hatch, Gary; Gordon, Terry

    2009-01-01

    Ozone (O3) is a respiratory irritant that leads to airway inflammation and pulmonary dysfunction. Animal studies show that neonates are more sensitive to O3 inhalation than adults, and children represent a potentially susceptible population. This latter notion is not well established, and biological mechanisms underlying a predisposition to pollution-induced pulmonary effects are unknown. We examined age and strain as interactive factors affecting differential pulmonary responses to inhaled O3. Male and female adult mice (15 weeks old) and neonates (15–16 days old) from eight genetically diverse inbred strains were exposed to 0.8 ppm O3 for 5 h. Pulmonary injury and lung inflammation were quantified as total protein concentration and total polymorphonuclear neutrophil (PMN) number in lavage fluid recovered 24-h postexposure. Dose-response and time-course curves were generated using SJL/J pups, and 18O lung burden dose was assessed in additional mice. Interstrain differences in response to O3 were seen in neonatal mice: Balb/cJ and SJL/J being most sensitive and A/J and 129x1/SvJ most resistant. The PMN response to O3 was greater in neonates than in adults, specifically for SJL/J and C3H/HeJ strains, independent of dose. Small gender differences were also observed in adult mice. Variation in protein concentrations and PMN counts between adults and pups were strain dependent, suggesting that genetic determinants do play a role in age-related sensitivity to O3. Further research will help to determine what genetic factors contribute to these heightened responses, and to quantify the relative contribution of genes vs. environment in O3-induced health effects. PMID:19066396

  11. Novel Mode of Defective Neural Tube Closure in the Non-Obese Diabetic (NOD) Mouse Strain

    PubMed Central

    Salbaum, J. Michael; Kruger, Claudia; MacGowan, Jacalyn; Herion, Nils J.; Burk, David; Kappen, Claudia

    2015-01-01

    Failure to close the neural tube results in birth defects, with severity ranging from spina bifida to lethal anencephaly. Few genetic risk factors for neural tube defects are known in humans, highlighting the critical role of environmental risk factors, such as maternal diabetes. Yet, it is not well understood how altered maternal metabolism interferes with embryonic development, and with neurulation in particular. We present evidence from two independent mouse models of diabetic pregnancy that identifies impaired migration of nascent mesodermal cells in the primitive streak as the morphogenetic basis underlying the pathogenesis of neural tube defects. We conclude that perturbed gastrulation not only explains the neurulation defects, but also provides a unifying etiology for the broad spectrum of congenital malformations in diabetic pregnancies. PMID:26593875

  12. Novel Mode of Defective Neural Tube Closure in the Non-Obese Diabetic (NOD) Mouse Strain.

    PubMed

    Salbaum, J Michael; Kruger, Claudia; MacGowan, Jacalyn; Herion, Nils J; Burk, David; Kappen, Claudia

    2015-01-01

    Failure to close the neural tube results in birth defects, with severity ranging from spina bifida to lethal anencephaly. Few genetic risk factors for neural tube defects are known in humans, highlighting the critical role of environmental risk factors, such as maternal diabetes. Yet, it is not well understood how altered maternal metabolism interferes with embryonic development, and with neurulation in particular. We present evidence from two independent mouse models of diabetic pregnancy that identifies impaired migration of nascent mesodermal cells in the primitive streak as the morphogenetic basis underlying the pathogenesis of neural tube defects. We conclude that perturbed gastrulation not only explains the neurulation defects, but also provides a unifying etiology for the broad spectrum of congenital malformations in diabetic pregnancies. PMID:26593875

  13. Sheltering behavior and locomotor activity in 11 genetically diverse common inbred mouse strains using home-cage monitoring.

    PubMed

    Loos, Maarten; Koopmans, Bastijn; Aarts, Emmeke; Maroteaux, Gregoire; van der Sluis, Sophie; Verhage, Matthijs; Smit, August B

    2014-01-01

    Functional genetic analyses in mice rely on efficient and in-depth characterization of the behavioral spectrum. Automated home-cage observation can provide a systematic and efficient screening method to detect unexplored, novel behavioral phenotypes. Here, we analyzed high-throughput automated home-cage data using existing and novel concepts, to detect a plethora of genetic differences in spontaneous behavior in a panel of commonly used inbred strains (129S1/SvImJ, A/J, C3H/HeJ, C57BL/6J, BALB/cJ, DBA/2J, NOD/LtJ, FVB/NJ, WSB/EiJ, PWK/PhJ and CAST/EiJ). Continuous video-tracking observations of sheltering behavior and locomotor activity were segmented into distinguishable behavioral elements, and studied at different time scales, yielding a set of 115 behavioral parameters of which 105 showed highly significant strain differences. This set of 115 parameters was highly dimensional; principal component analysis identified 26 orthogonal components with eigenvalues above one. Especially novel parameters of sheltering behavior and parameters describing aspects of motion of the mouse in the home-cage showed high genetic effect sizes. Multi-day habituation curves and patterns of behavior surrounding dark/light phase transitions showed striking strain differences, albeit with lower genetic effect sizes. This spontaneous home-cage behavior study demonstrates high dimensionality, with a strong genetic contribution to specific sets of behavioral measures. Importantly, spontaneous home-cage behavior analysis detects genetic effects that cannot be studied in conventional behavioral tests, showing that the inclusion of a few days of undisturbed, labor extensive home-cage assessment may greatly aid gene function analyses and drug target discovery. PMID:25264768

  14. Sheltering Behavior and Locomotor Activity in 11 Genetically Diverse Common Inbred Mouse Strains Using Home-Cage Monitoring

    PubMed Central

    Aarts, Emmeke; Maroteaux, Gregoire; van der Sluis, Sophie

    2014-01-01

    Functional genetic analyses in mice rely on efficient and in-depth characterization of the behavioral spectrum. Automated home-cage observation can provide a systematic and efficient screening method to detect unexplored, novel behavioral phenotypes. Here, we analyzed high-throughput automated home-cage data using existing and novel concepts, to detect a plethora of genetic differences in spontaneous behavior in a panel of commonly used inbred strains (129S1/SvImJ, A/J, C3H/HeJ, C57BL/6J, BALB/cJ, DBA/2J, NOD/LtJ, FVB/NJ, WSB/EiJ, PWK/PhJ and CAST/EiJ). Continuous video-tracking observations of sheltering behavior and locomotor activity were segmented into distinguishable behavioral elements, and studied at different time scales, yielding a set of 115 behavioral parameters of which 105 showed highly significant strain differences. This set of 115 parameters was highly dimensional; principal component analysis identified 26 orthogonal components with eigenvalues above one. Especially novel parameters of sheltering behavior and parameters describing aspects of motion of the mouse in the home-cage showed high genetic effect sizes. Multi-day habituation curves and patterns of behavior surrounding dark/light phase transitions showed striking strain differences, albeit with lower genetic effect sizes. This spontaneous home-cage behavior study demonstrates high dimensionality, with a strong genetic contribution to specific sets of behavioral measures. Importantly, spontaneous home-cage behavior analysis detects genetic effects that cannot be studied in conventional behavioral tests, showing that the inclusion of a few days of undisturbed, labor extensive home-cage assessment may greatly aid gene function analyses and drug target discovery. PMID:25264768

  15. Mouse genetic differences in voluntary wheel running, adult hippocampal neurogenesis and learning on the multi-strain-adapted plus water maze

    PubMed Central

    Merritt, Jennifer; Rhodes, Justin S.

    2014-01-01

    Moderate levels of aerobic exercise broadly enhance cognition throughout the lifespan. One hypothesized contributing mechanism is increased adult hippocampal neurogenesis. Recently, we measured the effects of voluntary wheel running on adult hippocampal neurogenesis in 12 different mouse strains, and found increased neurogenesis in all strains, ranging from 2 to 5 fold depending on the strain. The purpose of this study was to determine the extent to which increased neurogenesis from wheel running is associated with enhanced performance on the water maze for 5 of the 12 strains, chosen based on their levels of neurogenesis observed in the previous study (C57BL/6J, 129S1/SvImJ, B6129SF1/J, DBA/2J, and B6D2F1/J). Mice were housed with or without a running wheels for 30 days then tested for learning and memory on the plus water maze, adapted for multiple strains, and rotarod test of motor performance. The first 10 days, animals were injected with BrdU to label dividing cells. After behavioral testing animals were euthanized to measure adult hippocampal neurogenesis using standard methods. Levels of neurogenesis depended on strain but all mice had a similar increase in neurogenesis in response to exercise. All mice acquired the water maze but performance depended on strain. Exercise improved water maze performance in all strains to a similar degree. Rotarod performance depended on strain. Exercise improved rotarod performance only in DBA/2J and B6D2F1/J mice. Taken together, results demonstrate that despite different levels of neurogenesis, memory performance and motor coordination in these mouse strains, all strains have the capacity to increase neurogenesis and improve learning on the water maze through voluntary wheel running. PMID:25435316

  16. Effect of Mouse Strain in a Model of Chemical-induced Respiratory Allergy

    PubMed Central

    Nishino, Risako; Fukuyama, Tomoki; Watanabe, Yuko; Kurosawa, Yoshimi; Ueda, Hideo; Kosaka, Tadashi

    2014-01-01

    The inhalation of many types of chemicals is a leading cause of allergic respiratory diseases, and effective protocols are needed for the detection of environmental chemical–related respiratory allergies. In our previous studies, we developed a method for detecting environmental chemical–related respiratory allergens by using a long-term sensitization–challenge protocol involving BALB/c mice. In the current study, we sought to improve our model by characterizing strain-associated differences in respiratory allergic reactions to the well-known chemical respiratory allergen glutaraldehyde (GA). According to our protocol, BALB/c, NC/Nga, C3H/HeN, C57BL/6N, and CBA/J mice were sensitized dermally with GA for 3 weeks and then challenged with intratracheal or inhaled GA at 2 weeks after the last sensitization. The day after the final challenge, all mice were euthanized, and total serum IgE levels were assayed. In addition, immunocyte counts, cytokine production, and chemokine levels in the hilar lymph nodes (LNs) and bronchoalveolar lavage fluids (BALF) were also assessed. In conclusion, BALB/c and NC/Nga mice demonstrated markedly increased IgE reactions. Inflammatory cell counts in BALF were increased in the treated groups of all strains, especially BALB/c, NC/Nga, and CBA/J strains. Cytokine levels in LNs were increased in all treated groups except for C3H/HeN and were particularly high in BALB/c and NC/Nga mice. According to our results, we suggest that BALB/c and NC/Nga are highly susceptible to respiratory allergic responses and therefore are good candidates for use in our model for detecting environmental chemical respiratory allergens. PMID:25048268

  17. Regional brain volumes changes in adult male FMR1-KO mouse on the FVB strain.

    PubMed

    Lai, J K Y; Lerch, J P; Doering, L C; Foster, J A; Ellegood, J

    2016-03-24

    Fragile X Syndrome (FXS) is the most common heritable single gene cause of autism spectrum disorder (ASD). FMR1-KO mice mimic the etiology and phenotypic manifestations of FXS. Neuroanatomical changes in specific brain regions have been reported in clinical settings and in preclinical models. FMR1-KO mice have been generated in different strains including C57Bl/6 (B6) and FVB. Mice on different genetic backgrounds have stable yet distinct behavioral phenotypes that may lead to unique gene-strain interactions on brain structure. Previous magnetic resonance imaging (MRI) studies have examined FMR1 knockout male mice on a B6 and found few differences compared to wild-type mice. Here, we examine brain volumes in FMR1 knockout male mice on a FVB background using high resolution (multi-channel 7.0Tesla) MRI. We observe multiple differences in the neuroanatomy of male FMR1-/y mice on a FVB background. Significantly larger relative volume (% total brain volume) differences were found in major white matter structures throughout the brain. In addition, there were changes in areas associated with fronto-striatal circuitry and other regions. Functional and structural connectivity differences are often seen in human ASD, and therefore, this increased white matter seen in the FMR1-KO-FVB could be highlighting a structural over-connectivity, which could lead to some of the behavioral abnormalities seen with the FMR1-KO-FVB mice. Furthermore, these results highlight the importance of genetic strain contribution to brain structure. PMID:26794591

  18. Strain differences in the attenuation of bone accrual in a young growing mouse model of insulin resistance.

    PubMed

    Rendina-Ruedy, Elizabeth; Graef, Jennifer L; Davis, McKale R; Hembree, Kelsey D; Gimble, Jeffrey M; Clarke, Stephen L; Lucas, Edralin A; Smith, Brenda J

    2016-07-01

    Skeletal fractures are considered a chronic complication of type 2 diabetes mellitus (T2DM), but the etiology of compromised bone quality that develops over time remains uncertain. This study investigated the concurrent alterations in metabolic and skeletal changes in two mouse strains, a responsive (C57BL/6) and a relatively resistant (C3H/HeJ) strain, to high-fat diet-induced glucose intolerance. Four-week-old male C57BL/6 and C3H/HeJ mice were randomized to a control (Con = 10 % kcal fat) or high-fat (HF = 60 % kcal fat) diet for 2, 8, or 16 weeks. Metabolic changes, including blood glucose, plasma insulin and leptin, and glucose tolerance were monitored over time in conjunction with alterations in bone structure and turn over. Elevated fasting glucose occurred in both the C57BL/6 and C3H/HeJ strains on the HF diet at 2 and 8 weeks, but only in the C57BL/6 strain at 16 weeks. Both strains on the HF diet demonstrated impaired glucose tolerance at each time point. The C57BL/6 mice on the HF diet exhibited lower whole-body bone mineral density (BMD) by 8 and 16 weeks, but the C3H/HeJ strain had no evidence of bone loss until 16 weeks. Analyses of bone microarchitecture revealed that trabecular bone accrual in the distal femur metaphysis was attenuated in the C57BL/6 mice on the HF diet at 8 and 16 weeks. In contrast, the C3H/HeJ mice were protected from the deleterious effects of the HF diet on trabecular bone. Alterations in gene expression from the femur revealed that several toll-like receptor (TLR)-4 targets (Atf4, Socs3, and Tlr4) were regulated by the HF diet in the C57BL/6 strain, but not in the C3H/HeJ strain. Structural changes observed only in the C57BL/6 mice were accompanied with a decrease in osteoblastogenesis after 8 and 16 weeks on the HF diet, suggesting a TLR-4-mediated mechanism in the suppression of bone formation. Both the C57BL/6 and C3H/HeJ mice demonstrated an increase in osteoclastogenesis after 8 weeks on the HF diet; however

  19. A novel anesthesia regime enables neurofunctional studies and imaging genetics across mouse strains.

    PubMed

    Petrinovic, Marija M; Hankov, Georges; Schroeter, Aileen; Bruns, Andreas; Rudin, Markus; von Kienlin, Markus; Künnecke, Basil; Mueggler, Thomas

    2016-01-01

    Functional magnetic resonance imaging (fMRI) has revolutionized neuroscience by opening a unique window that allows neurocircuitry function and pathological alterations to be probed non-invasively across brain disorders. Here we report a novel sustainable anesthesia procedure for small animal neuroimaging that overcomes shortcomings of anesthetics commonly used in rodent fMRI. The significantly improved preservation of cerebrovascular dynamics enhances sensitivity to neural activity changes for which it serves as a proxy in fMRI readouts. Excellent cross-species/strain applicability provides coherence among preclinical findings and is expected to improve translation to clinical fMRI investigations. The novel anesthesia procedure based on the GABAergic anesthetic etomidate was extensively validated in fMRI studies conducted in a range of genetically engineered rodent models of autism and strains commonly used for transgenic manipulations. Etomidate proved effective, yielded long-term stable physiology with basal cerebral blood flow of ~0.5 ml/g/min and full recovery. Cerebrovascular responsiveness of up to 180% was maintained as demonstrated with perfusion- and BOLD-based fMRI upon hypercapnic, pharmacological and sensory stimulation. Hence, etomidate lends itself as an anesthetic-of-choice for translational neuroimaging studies across rodent models of brain disorders. PMID:27080031

  20. A novel anesthesia regime enables neurofunctional studies and imaging genetics across mouse strains

    PubMed Central

    Petrinovic, Marija M.; Hankov, Georges; Schroeter, Aileen; Bruns, Andreas; Rudin, Markus; von Kienlin, Markus; Künnecke, Basil; Mueggler, Thomas

    2016-01-01

    Functional magnetic resonance imaging (fMRI) has revolutionized neuroscience by opening a unique window that allows neurocircuitry function and pathological alterations to be probed non-invasively across brain disorders. Here we report a novel sustainable anesthesia procedure for small animal neuroimaging that overcomes shortcomings of anesthetics commonly used in rodent fMRI. The significantly improved preservation of cerebrovascular dynamics enhances sensitivity to neural activity changes for which it serves as a proxy in fMRI readouts. Excellent cross-species/strain applicability provides coherence among preclinical findings and is expected to improve translation to clinical fMRI investigations. The novel anesthesia procedure based on the GABAergic anesthetic etomidate was extensively validated in fMRI studies conducted in a range of genetically engineered rodent models of autism and strains commonly used for transgenic manipulations. Etomidate proved effective, yielded long-term stable physiology with basal cerebral blood flow of ~0.5 ml/g/min and full recovery. Cerebrovascular responsiveness of up to 180% was maintained as demonstrated with perfusion- and BOLD-based fMRI upon hypercapnic, pharmacological and sensory stimulation. Hence, etomidate lends itself as an anesthetic-of-choice for translational neuroimaging studies across rodent models of brain disorders. PMID:27080031

  1. [Anti-aging studies on the senescence accelerated mouse (SAM) strains].

    PubMed

    Takahashi, Ryoya

    2010-01-01

    Senescence accelerated mouse (SAM), a murine model of accelerated senescence, was established by Toshio Takeda and colleagues. SAM consists of series of SAMP (prone) and SAMR (resistant) lines. All SAMP lines (from SAMP1 to SAMP11) are characterized by accelerated accumulation of senile features, earlier onset and faster progress of age-associated pathological phenotypes, such as amyloidosis, impaired immune response, senile osteoporosis and deficits in learning and memory. These SAMP lines are useful for evaluation of putative anti-aging therapies. For example, SAMP1 line is used to study the anti-aging effect of the antioxidant containing foods and various anti-oxidants, such as coenzyme Q10, vitamin C, lycopene. SAMP8 line exhibiting an early onset of impaired learning and memory is often used for test strategies for therapeutic intervention of dementia of early onset. SAMP6 is used as an animal model for developing new strategies for the treatment of osteoporosis in humans. Various lines of SAM (P1, P6, P8, P10 and R1) are now commercially available for research. In this review, I will briefly introduce various usages of SAM in anti-aging research. PMID:20046059

  2. Optical measurement of mouse strain differences in cerebral blood flow using indocyanine green

    PubMed Central

    Kang, Hye-Min; Sohn, Inkyung; Kim, Seunggyu; Kim, Daehwan; Jung, Junyang; Jeong, Joo-Won; Park, Chan

    2015-01-01

    C57BL/6 mice have more cerebral arterial branches and collaterals than BALB/c mice. We measured and compared blood flow dynamics of the middle cerebral artery (MCA) in these two strains, using noninvasive optical imaging with indocyanine green (ICG). Relative maximum fluorescence intensity (Imax) and the time needed for ICG to reach Imax in the MCA of C57BL/c were lower than that in BALB/c mice. Moreover, the mean transit time was significantly lower in C57BL/6 than in BALB/c mice. These data suggest that the higher number of arterial branches and collaterals in C57BL/6 mice yields a lower blood flow per cerebral artery. PMID:25833343

  3. Gene expression in the mouse eye: an online resource for genetics using 103 strains of mice

    PubMed Central

    Lu, Lu; Freeman-Anderson, Natalie E.; Templeton, Justin P.; Nassr, Mohamed; Wang, Xusheng; Gu, Weikuan; Jiao, Yan; Williams, Robert W.

    2009-01-01

    Purpose Individual differences in patterns of gene expression account for much of the diversity of ocular phenotypes and variation in disease risk. We examined the causes of expression differences, and in their linkage to sequence variants, functional differences, and ocular pathophysiology. Methods mRNAs from young adult eyes were hybridized to oligomer microarrays (Affymetrix M430v2). Data were embedded in GeneNetwork with millions of single nucleotide polymorphisms, custom array annotation, and information on complementary cellular, functional, and behavioral traits. The data include male and female samples from 28 common strains, 68 BXD recombinant inbred lines, as well as several mutants and knockouts. Results We provide a fully integrated resource to map, graph, analyze, and test causes and correlations of differences in gene expression in the eye. Covariance in mRNA expression can be used to infer gene function, extract signatures for different cells or tissues, to define molecular networks, and to map quantitative trait loci that produce expression differences. These data can also be used to connect disease phenotypes with sequence variants. We demonstrate that variation in rhodopsin expression efficiently predicts candidate genes for eight uncloned retinal diseases, including WDR17 for the human RP29 locus. Conclusions The high level of strain variation in gene expression is a powerful tool that can be used to explore and test molecular networks underlying variation in structure, function, and disease susceptibility. The integration of these data into GeneNetwork provides users with a workbench to test linkages between sequence differences and eye structure and function. PMID:19727342

  4. Rolling Nagoya mouse strain (PROD-rol/rol) with classic piebald mutation.

    PubMed

    Yoshimoto, Takuro; Aoyama, Yo; Kim, Tae Yeon; Niimi, Kimie; Takahashi, Eiki; Itakura, Chitoshi

    2014-08-01

    Ataxic rolling Nagoya (PROD-rol/rol) mice, which carry a mutation in the α1 subunit of the Cav2.1 channel (Cacna1a) gene, were discovered in 1969. They show white spots on agouti coat and have a mutation in the piebald spotting (s) locus. However, mutation analysis of the s locus encoding the endothelin receptor type B (Ednrb) gene in PROD-rol/rol mice had not been performed. Here, we examined the genomic and mRNA sequences of the Ednrb gene in PROD-rol/rol and wild-type rolling Nagoya (PROD-s/s) and studied the expression patterns of Ednrb and Cacna1a genes in these mice in comparison with C57BL/6J mice. Polymerase chain reaction analyses revealed two silent nucleotide substitutions in the coding region and insertion of a retroposon-like element in intron 1 of the Ednrb gene. Expression analyses demonstrated similar localizations and levels of Ednrb and Cacna1a expression in the colon between PROD-rol/rol and PROD-s/s mice, but the expression levels of both genes were diminished compared with C57BL/6J mice. Microsatellite genotyping showed that at least particular regions of chromosome 14 proximal to the Ednrb locus of the PROD strain were derived from Japanese fancy piebald mice. These results indicated that PROD-rol/rol mice have two mutant genes, Ednrb and Cacna1a. As no PROD strain had an intact Ednrb gene, using congenic rolling mice would better serve to examine rolling Nagoya-type Cav2.1 channel dysfunctions. PMID:24758835

  5. Significant effects of sex, strain, and anesthesia in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy.

    PubMed

    Twele, Friederike; Töllner, Kathrin; Brandt, Claudia; Löscher, Wolfgang

    2016-02-01

    The intrahippocampal kainate mouse model of mesial temporal lobe epilepsy is increasingly being used for studies on epileptogenesis and antiepileptogenesis. Almost all previous studies used male mice for this purpose, and no study is available in this or other models of acquired epilepsy that directly compared epileptogenesis in female and male rodents. Epidemiological studies suggest that gender may affect susceptibility to epilepsy and its prognosis; therefore, one goal of this study was to investigate whether sex has an influence on latent period and epileptogenesis in the intrahippocampal kainate model in mice. Another aspect that was examined in the present study was whether mouse strain differences in epileptogenesis exist. Finally, we examined the effects of different types of anesthesia (chloral hydrate, isoflurane) on kainate-induced status epilepticus (SE) and epileptogenesis. Continuous (24/7) video-EEG monitoring was used during SE and the 2 weeks following SE as well as 4-6 weeks after SE. In male NMRI mice with chloral hydrate anesthesia during kainate injection, SE was followed by a seizure-free latent period of 10-14 days if hippocampal paroxysmal discharges (HPDs) recorded from the kainate focus were considered the onset of epilepsy. Anesthesia with isoflurane led to a more rapid onset and higher severity of SE, and not all male NMRI mice exhibited a seizure-free latent period. Female NMRI mice differed from male animals in the lack of any clear latent period, independently of anesthesia type. Furthermore, HPDs were only rarely observed. These problems were not resolved by decreasing the dose of kainate or using other strains (C57BL/6, FVB/N) of female mice. The present data are the first to demonstrate marked sex-related differences in the latent period following brain injury in a rodent model of acquired epilepsy. Furthermore, our data demonstrate that the choice of anesthestic agent during kainate administration affects SE severity and as a

  6. Mouse strain and conditioning regimen determine survival and function of human leucocytes in immunodeficient mice

    PubMed Central

    Tournoy, K G; Depraetere, S; Pauwels, R A; Leroux-Roels, G G

    2000-01-01

    The innate immune system of severe combined immunodeficient (SCID) mice represents an important barrier to the successful engraftment of human cells. Different genetic and pharmacological strategies improve the graft survival. Non-obese diabetic (NOD)-SCID mice are better hosts for reconstitution with human peripheral blood leucocytes (Hu-PBL) because of their reduced natural killer cell and macrophage activity next to defective T and B cell functions. We investigated effects of TM-β1, a rat monoclonal antibody recognizing the mouse IL-2 receptor β-chain, on Hu-PBL survival and function in NOD-SCID and SCID mice. Relative to untreated littermates, TM-β1 improved Hu-PBL survival in SCID and NOD-SCID mice. Moreover, TM-β1-pretreated NOD-SCID mice displayed significantly better Hu-PBL survival and tissue distribution than TM-β1-pretreated SCID mice. Irradiation of NOD-SCID mice further enhanced the effects of TM-β1. However, these animals died within 3 weeks post-grafting due to graft-versus-host disease. Secondary immune responses were evaluated with Hu-PBL from a donor immune to hepatitis B surface antigen (HBsAg). In TM-β1-pretreated NOD-SCID mice, human HBsAg-specific memory B cells produced high titres of anti-HBsAg immunoglobulin irrespective of the administration of a secondary antigen booster dose. This contrasts with secondary immune responses in TM-β1-pretreated SCID mice where high titred antigen-specific immunoglobulins were produced when the appropriate antigen booster was given. In conclusion, reducing the function of the innate immune system in immunodeficient mice improves survival of the human graft and can result in an activation of the memory B cells without the need for recall antigen exposure. PMID:10606988

  7. Differences in susceptibility among mouse strains to infection with Plasmodium berghei (ANKA clone) sporozoites and its relationship to protection by gamma-irradiated sporozoites

    SciTech Connect

    Jaffe, R.I.; Lowell, G.H.; Gordon, D.M. )

    1990-04-01

    Three inbred mouse strains, C57BL/6 (H-2b), A/J (H-2a), and BALB/c (H-2d), and 1 outbred strain, CD-1, demonstrated differences in susceptibility to iv challenge with the ANKA clone of Plasmodium berghei. Mice were challenged with 100, 1,000, or 10,000 sporozoites, then evaluated daily beginning on day 4 for patency. CD-1 mice were further evaluated at challenge doses of 12,500, 25,000, and 50,000 sporozoites. C57BL/6 mice were the easiest to infect, with 90% becoming infected with 100 sporozoites. The outbred strain CD-1 was the most difficult to infect, requiring a challenge dose of 25,000 sporozoites/mouse in order to achieve a 100% infection rate. Mouse strains also demonstrated differences in their ability to be protected by intravenous immunization with gamma-irradiated sporozoites. A/J mice needed a minimum of 3 doses of irradiated sporozoites for protection against a challenge with 10,000 sporozoites. In contrast, BALB/c mice immunized with a single dose of 1,000 irradiated sporozoites are protected against a 10,000 sporozoite challenge. These data suggest that both infectivity and protection are genetically restricted and that susceptibility to infection may be inversely related to protection.

  8. Differences in susceptibility among mouse strains to infection with Plasmodium berghei (ANKA clone) sporozoites and its relationship to protection by gamma-irradiated sporozoites

    SciTech Connect

    Jaffe, R.I.; Lowell, G.H.; Gordon, D.M.

    1990-01-01

    Three inbred mouse strains, C57BL/6 (H-2/b/), A/J (H-2/a/), and BALB/C (H-2/d/), and one outbred strain, CD-1, demonstrated differences in susceptibility to challenge intravenously with the ANKA clone of Plasmodium berghei. Mice were challenged with 100, 1000, or 10000 sporozoites, then evaluated daily beginning on day 4 for patency. CD-1 mice were further evaluated at challenge doses of 125000, 25000, and 50000 sporozoites. C57BL/6 mice were the easiest to infect with 90% becoming infected with 100 sporozoites. The outbred strain CD-1 was the most difficult to infect requiring a challenge dose of 25000 sporozoites per mouse in order to achieve a 100% infection rate. Mouse strains also demonstrated differences in their ability to be protected by intravenous immunization with gamma-irradiated sporozoites. A/J mice needed a minimum of 3 doses of irradiated sporozoites for protection against a challenge with 1000 sporozoites. In contrast BALB/C mice, immunized with a single dose of 1000 irradiated sporozoites, are protected against a 10000 sporozoite challenge. These data suggest that both infectivity and protection are genetically restricted and that susceptibility to infection may be inversely related to protection.

  9. MOUSE STRAIN-DEPENDENT CASPASE ACTIVATION DURING ACETAMINOPHEN HEPATOTOXICITY DOES NOT RESULT IN APOPTOSIS OR MODULATION OF INFLAMMATION

    PubMed Central

    Williams, C. David; Koerner, Michael R.; Lampe, Jed N.; Farhood, Anwar; Jaeschke, Hartmut

    2011-01-01

    The mechanisms of acetaminophen (APAP)-mediated hepatic oncotic necrosis have been extensively characterized. However, it was recently demonstrated that fed CD-1 mice have a transient caspase activation which initiates apoptosis. To evaluate these findings in more detail, outbred (Swiss Webster, SW) and inbred (C57BL/6) mice were treated with APAP with or without pan-caspase inhibitor and compared to the apoptosis model of galactosamine (GalN)/endotoxin (ET). Fasted or fed APAP-treated C57BL/6 mice showed no evidence of caspase-3 processing or activity. Interestingly, a minor, temporary increase in caspase-3 processing and activity (150% above baseline) was observed after APAP treatment only in fed SW mice. The degree of caspase-3 activation in SW mice after APAP was minor compared to that observed in GalN/ET-treated mice (1600% above baseline). The pancaspase inhibitor attenuated caspase activation and resulted in increased APAP-induced injury (plasma ALT, necrosis scoring). The caspase inhibitor did not affect apoptosis because regardless of treatment only <0.5% of hepatocytes showed consistent apoptotic morphology after APAP. In contrast, >20% apoptotic cells were observed in GalN/ET-treated mice. Presence of the caspase inhibitor altered hepatic glutathione levels in SW mice, which could explain the exacerbation of injury. Additionally, the infiltration of hepatic neutrophils was not altered by the fed state of either mouse strain. Conclusion: Minor caspase-3 activation without apoptotic cell death can be observed only in fed mice of some outbred strains. These findings suggest that although the severity of APAP-induced liver injury varies between fed and fasted animals, the mechanism of cell death does not fundamentally change. PMID:22023962

  10. Brain inflammation, neurodegeneration and seizure development following picornavirus infection markedly differ among virus and mouse strains and substrains.

    PubMed

    Bröer, Sonja; Käufer, Christopher; Haist, Verena; Li, Lin; Gerhauser, Ingo; Anjum, Muneeb; Bankstahl, Marion; Baumgärtner, Wolfgang; Löscher, Wolfgang

    2016-05-01

    Infections, particularly those caused by viruses, are among the main causes of acquired epilepsy, but the mechanisms causing epileptogenesis are only poorly understood. As a consequence, no treatment exists for preventing epilepsy in patients at risk. Animal models are useful to study epileptogenesis after virus-induced encephalitis and how to interfere with this process, but most viruses that cause encephalitis in rodents are associated with high mortality, so that the processes leading to epilepsy cannot be investigated. Recently, intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6 (B6) mice was reported to induce early seizures and epilepsy and it was proposed that the TMEV mouse model represents the first virus infection-driven animal model of epilepsy. In the present study, we characterized this model in two B6 substrains and seizure-resistant SJL/J mice by using three TMEV (sub)strains (BeAn-1, BeAn-2, DA). The idea behind this approach was to study what is and what is not necessary for development of acute and late seizures after brain infection in mice. Receiver operating characteristic (ROC) curve analysis was used to determine which virus-induced brain alterations are associated with seizure development. In B6 mice infected with different TMEV virus (sub)strains, the severity of hippocampal neurodegeneration, amount of MAC3-positive microglia/macrophages, and expression of the interferon-inducible antiviral effector ISG15 were almost perfect at discriminating seizing from non-seizing B6 mice, whereas T-lymphocyte brain infiltration was not found to be a crucial factor. However, intense microglia/macrophage activation and some hippocampal damage were also observed in SJL/J mice. Overall, the TMEV model provides a unique platform to study virus and host factors in ictogenesis and epileptogenesis. PMID:26892877

  11. Impaired Pavlovian fear extinction is a common phenotype across genetic lineages of the 129 inbred mouse strain

    PubMed Central

    Camp, Marguerite; Norcross, Maxine; Whittle, Nigel; Feyder, Michael; D’Hanis, Wolfgang; Yilmazer-Hanke, Deniz; Singewald, Nicolas; Holmes, Andrew

    2009-01-01

    Fear extinction is impaired in psychiatric disorders such as posttraumatic stress disorder and schizophrenia, which have a major genetic component. However, the genetic factors underlying individual variability in fear extinction remain to be determined. By comparing a panel of inbred mouse strains, we recently identified a strain, 129S1/SvImJ (129S1), that exhibits a profound and selective deficit in Pavlovian fear extinction, and associated abnormalities in functional activation of a key prefrontal-amygdala circuit, as compared to C57BL/6J. The first aim of the present study was to assess fear extinction across multiple 129 substrains representing the strain’s four different genetic lineages (Parental, Steel, Teratoma, Contaminated). Results showed that 129P1/ReJ, 129P3/J, 129T2/SvEmsJ, and 129X1/SvJ exhibited poor fear extinction, relative to C57BL/6J, while 129S1 showed evidence of fear incubation. Based on these results, the second aim was to further characterize the nature and specificity of the extinction phenotype in 129S1, as an exemplar of the 129 substrains. Results showed that the extinction deficit in 129S1 was neither the result of a failure to habituate to a sensitized fear response, nor an artifact of a fear response to (unconditioned) tone per se. A stronger conditioning protocol (i.e., five × higher intensity shocks) produced an increase in fear expression in 129S1, relative to C57BL/6J, due to rapid rise in freezing during tone presentation. Taken together, these data demonstrate that impaired fear extinction is a phenotypic feature common across 129 substrains, and provide preliminary evidence that impaired fear extinction in 129S1 may be reflect a pro-fear incubation-like process. PMID:19674120

  12. Divergent neuroactive steroid responses to stress and ethanol in rat and mouse strains: Relevance for human studies

    PubMed Central

    Porcu, Patrizia; Morrow, A. Leslie

    2014-01-01

    Rationale Neuroactive steroids are endogenous or synthetic steroids that rapidly alter neuronal excitability via membrane receptors, primarily GABAA receptors. Neuroactive steroids regulate many physiological processes including hypothalamic-pituitary-adrenal (HPA) axis function, ovarian cycle, pregnancy, aging, and reward. Moreover, alterations in neuroactive steroid synthesis are implicated in several neuropsychiatric disorders. Objectives This review will summarize the pharmacological properties and physiological regulation of neuroactive steroids, with a particular focus on divergent neuroactive steroid responses to stress and ethanol in rats, mice and humans. Results GABAergic neuroactive steroids exert a homeostatic regulation of the HPA axis in rats and humans, whereby the increase in neuroactive steroid levels following acute stress counteracts HPA axis hyperactivity and restores homeostasis. In contrast, in C57BL/6J mice, acute stress decreases neurosteroidogenesis and neuroactive steroids exert paradoxical excitatory effects upon the HPA axis. Rats, mice and humans also differ in the neuroactive steroid responses to ethanol. Genetic variation in neurosteroidogenesis may explain the different neuroactive steroid responses to stress or ethanol. Conclusions Rats and mouse strains show divergent effects of stress and ethanol on neuroactive steroids in both plasma and brain. The study of genetic variation in the various processes that determine neuroactive steroids levels as well as their effects on cell signaling may underlie these differences and may play a relevant role for the potential therapeutic benefits of neuroactive steroids. PMID:24770626

  13. The SAMP1/YitFc Mouse Strain: A Spontaneous Model of Crohn’s Disease-Like Ileitis

    PubMed Central

    Pizarro, Theresa T.; Pastorelli, Luca; Bamias, Giorgos; Garg, Rekha R.; Reuter, Brian K.; Mercado, Joseph R.; Chieppa, Marcello; Arseneau, Kristen O; Ley, Klaus; Cominelli, Fabio

    2011-01-01

    The SAMP1/YitFc mouse strain represents a model of Crohn’s disease (CD)-like ileitis that is ideal for investigating the pathogenesis of chronic intestinal inflammation. Differently from the vast majority of animal models of colitis, the ileal-specific phenotype characteristic of SAMP1/YitFc mice occurs spontaneously, without genetic, chemical or immunological manipulation. In addition, SAMP1/YitFc mice possess remarkable similarities to the human condition in regard to disease location, histologic features, incidence of extra-intestinal manifestations, and response to conventional therapies. SAMP1/YitFc mice also display a well-defined time course of a pre-disease state, and phases of acute and chronic ileitis. As such, the SAMP1/YitFc model is particularly suitable for elucidating pathways that precede the clinical phenotype that may lead to preventive, and therefore more efficacious, intervention with the natural course of disease, or alternatively, for the development of therapeutic strategies directed against chronic, established ileitis. In the following review, we summarize important contributions made by our group and others that uncover potential mechanisms in the pathogenesis of CD using this unique murine model of chronic intestinal inflammation. PMID:21557393

  14. COLONIZATION POTENTIALS OF MALE AND FEMALE E. COLI K 12 STRAINS E COLI B AND HUMAN FECAL E. COLI STRAINS IN THE MOUSE GI TRACT

    EPA Science Inventory

    In order to compare the colonization potentials of individual Escherichia coli strains, the authors developed a simple animal system in which both freshly isolated human strains and laboratory strains (i.e. E. coli B and E. coli K 12 strains) survive in the large intestine for lo...

  15. Mouse strain-dependent caspase activation during acetaminophen hepatotoxicity does not result in apoptosis or modulation of inflammation

    SciTech Connect

    Williams, C. David; Koerner, Michael R.; Lampe, Jed N.; Farhood, Anwar; Jaeschke, Hartmut

    2011-12-15

    The mechanisms of acetaminophen (APAP)-mediated hepatic oncotic necrosis have been extensively characterized. However, it was recently demonstrated that fed CD-1 mice have a transient caspase activation which initiates apoptosis. To evaluate these findings in more detail, outbred (Swiss Webster, SW) and inbred (C57BL/6) mice were treated with APAP with or without pan-caspase inhibitor and compared to the apoptosis model of galactosamine (GalN)/endotoxin (ET). Fasted or fed APAP-treated C57BL/6 mice showed no evidence of caspase-3 processing or activity. Interestingly, a minor, temporary increase in caspase-3 processing and activity (150% above baseline) was observed after APAP treatment only in fed SW mice. The degree of caspase-3 activation in SW mice after APAP was minor compared to that observed in GalN/ET-treated mice (1600% above baseline). The pancaspase inhibitor attenuated caspase activation and resulted in increased APAP-induced injury (plasma ALT, necrosis scoring). The caspase inhibitor did not affect apoptosis because regardless of treatment only < 0.5% of hepatocytes showed consistent apoptotic morphology after APAP. In contrast, > 20% apoptotic cells were observed in GalN/ET-treated mice. Presence of the caspase inhibitor altered hepatic glutathione levels in SW mice, which could explain the exacerbation of injury. Additionally, the infiltration of hepatic neutrophils was not altered by the fed state of either mouse strain. Conclusion: Minor caspase-3 activation without apoptotic cell death can be observed only in fed mice of some outbred strains. These findings suggest that although the severity of APAP-induced liver injury varies between fed and fasted animals, the mechanism of cell death does not fundamentally change. -- Highlights: Black-Right-Pointing-Pointer During acetaminophen overdose caspase-3 can be activated in fed mice of certain outbred strains. Black-Right-Pointing-Pointer Hepatic ATP levels are not the determining factor for caspase

  16. A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant

    PubMed Central

    Agnihothram, Sudhakar; Yount, Boyd L.; Donaldson, Eric F.; Huynh, Jeremy; Menachery, Vineet D.; Gralinski, Lisa E.; Graham, Rachel L.; Becker, Michelle M.; Tomar, Sakshi; Scobey, Trevor D.; Osswald, Heather L.; Whitmore, Alan; Gopal, Robin; Ghosh, Arun K.; Mesecar, Andrew; Zambon, Maria; Heise, Mark; Denison, Mark R.; Baric, Ralph S.

    2014-01-01

    ABSTRACT Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis. PMID:24667706

  17. GENETIC MAPPING OF VOCALIZATION TO A SERIES OF INCREASING ACUTE FOOTSHOCKS USING B6.A CONSOMIC AND B6.D2 CONGENIC MOUSE STRAINS

    SciTech Connect

    Matthews, Douglas B; Chesler, Elissa J; Cook, Melloni N.; Cockroft, Judy; Philip, Vivek M; Goldowitz, Daniel

    2008-01-01

    Footshock response is used to study biological functions in mammals. However, the genetics underlying variability in footshock sensitivity are not well understood. In the current studies, a panel of B6.A consomic mouse strains, two B6.D2 congenic mouse strains and the progenitor strains were screened for footshock sensitivity as measured by audible vocalization. It was found that A/J (A) mice and C57BL/6J (B6) mice with an A Chromosome 1 (Chr 1) were less sensitive to footshock compared to B6 animals. Furthermore, the offspring of Chr 1 consomic mice crossed with B6 mice had vocalization levels that were intermediate to A/J and B6 animals. A F2 mapping panel revealed two significant QTLs for footshock vocalization centered around D1Mit490 and D1Mit206 on Chr 1. The role of these Chr 1 loci in footshock sensitivity was confirmed in B6.D2 congenic mice. These data identify genetic regions involved in footshock sensitivity and establish additional mouse resources for use in investigating complex behaviors.

  18. Effect of interferons and poly(I):poly(C) on the pathogenesis of the diabetogenic variant of encephalomyocarditis virus in different mouse strains.

    PubMed

    Giron, D J; Agostini, H J; Thomas, D C

    1988-12-01

    Interferon (IFN) can either prevent or exacerbate the pathogenic effects of the diabetogenic variant of encephalomyocarditis (EMC-D) virus. The effect seen is dependent upon the mouse strain and the time of IFN administration. For example, IFN-alpha beta protects SWR/J but not ICR Swiss male mice against the diabetogenic effects of the virus. Administration of either IFN-alpha beta or the IFN-inducer poly(I):poly(C) 4 days post infection, results in an exacerbation of the infection in ICR Swiss and C57BL/6 male mice. Studies have been initiated to investigate the role of the IFN system in the pathogenesis of this virus infection. In this study IFNs or poly(I):poly(C) were administered to several mouse strains at 24 h before or 4 days after infection with EMC-D virus. The results of such treatment ranged from complete protection of the animals from the diabetogenic effects of the virus to exacerbation of the infection as reflected by the virus content in selected organs. The effect was dependent upon the mouse strain, the type of IFN, and the time of its administration in relation to virus infection. PMID:2466089

  19. 2-Aminofluorene metabolism and DNA adduct formation by mononuclear leukocytes from rapid and slow acetylator mouse strains.

    PubMed

    Levy, G N; Chung, J G; Weber, W W

    1994-02-01

    Following exposure of mice to the arylamine carcinogen 2-aminofluorene, DNA-carcinogen adducts can be found in the target tissues liver and bladder, and also in circulating leukocytes. Evidence is presented here that mouse mononuclear leukocytes (MNL) are capable of metabolizing 2-aminofluorene to DNA-binding metabolites which give rise to the adducts found in the MNL. Both lymphocytes and monocytes were able to acetylate arylamines during 18 h of culture. The degree of acetylation was determined by the N-acetyltransferase genotype of the mice as shown through use of acetylator congenic strains which differ only in the Nat-2 gene. Cultured MNL from rapid acetylator mice (C57BL/6J and A.B6-Natr) produced about twice as much N-acetylaminofluorene from 2-aminofluorene and 6- to 8-fold as much N-acetyl-p-aminobenzoic acid from p-aminobenzoic acid as cells from slow acetylator mice (B6.A-Nat(s) and A/J). Other differences in arylamine metabolism by MNL in culture were observed and shown to be due to genetic factors, currently unidentified, other than N-acetyltransferase. DNA adduct formation following incubation of MNL with the arylamine carcinogen 2-aminofluorene was related to both acetylation capacity and to other genetic metabolic factors in the mouse genome. MNL from rapid acetylator mice with the C57BL/6J background (B6) had 3-fold the DNA adduct levels of cells from the corresponding slow acetylator congenic (B6.A-Nat(s)). Similarly, MNL from rapid acetylator mice with the A/J background (A.B6-Natr) had twice the DNA adduct levels of those from their corresponding slow congenic (A). Adduct levels in MNL from C57BL/6J were nearly the same as those of MNL from A/J, again indicating the involvement of loci other than acetylation in DNA adduct formation. The finding of genetically dependent arylamine carcinogen metabolism and DNA adduct formation in cultured MNL suggests the possibility of using cultured MNL for assessing individual susceptibility to arylamine

  20. DNA variation and brain region-specific expression profiles exhibit different relationships between inbred mouse strains: implications for eQTL mapping studies

    PubMed Central

    Hovatta, Iiris; Zapala, Matthew A; Broide, Ron S; Schadt, Eric E; Libiger, Ondrej; Schork, Nicholas J; Lockhart, David J; Barlow, Carrolee

    2007-01-01

    Background Expression quantitative trait locus (eQTL) mapping is used to find loci that are responsible for the transcriptional activity of a particular gene. In recent eQTL studies, expression profiles were derived from either homogenized whole brain or collections of large brain regions. However, the brain is a very heterogeneous organ, and expression profiles of different brain regions vary significantly. Because of the importance and potential power of eQTL studies in identifying regulatory networks, we analyzed gene expression patterns in different brain regions from multiple inbred mouse strains and investigated the implications for the design and analysis of eQTL studies. Results Gene expression profiles of five brain regions in six inbred mouse strains were studied. Few genes exhibited a significant strain-specific expression pattern, whereas a large number of genes exhibited brain region-specific patterns. We constructed phylogenetic trees based on the expression relationships between the strains and compared them with a DNA-level relationship tree. The trees based on the expression of strain-specific genes were constant across brain regions and mirrored DNA-level variation. However, the trees based on region-specific genes exhibited a different set of strain relationships, depending on the brain region. An eQTL analysis showed enrichment of cis-acting regulators among strain-specific genes, whereas brain region-specific genes appear to be mainly regulated by trans-acting elements. Conclusion Our results suggest that many regulatory networks are highly brain region specific and indicate the importance of conducting eQTL mapping studies using data from brain regions or tissues that are physiologically and phenotypically relevant to the trait of interest. PMID:17324278

  1. A quantitative histological study of strain-dependent differences in the effects of irradiation on mouse lung during the intermediate and late phases

    SciTech Connect

    Sharplin, J.; Franko, A.J. )

    1989-07-01

    Strain differences in the intermediate and late phases of the radiation response of mouse lung were investigated histologically. The proportion of lung impairment in mice at 28 and 52 weeks postirradiation and in mice dying of respiratory insufficiency was assessed by scoring lung acini as nonfunctional due to lesions which obstructed airflow, or open and presumably functional. The nine strains tested were divided into three groups on the basis of the late fibrotic response. Group 1 mice, three C57 strains, developed extensive contracted fibrosis and usually showed enough damage to explain late deaths. Group 2, SWR, A, and BALB/c strains, developed foci of contracted fibrosis. Group 3, CBA and two C3H strains, did not form fibrotic scars. Mice in Groups 2 and 3 that died with no pleural effusions appeared to have insufficient late lung damage to account for respiratory distress. Problems with pulmonary blood flow were indicated by evidence of loss of fine vasculature and right ventricular hypertrophy. In nondistressed, late-stage mice in Groups 2 and 3, loss of capillary perfusion in lung parenchyma free of obvious lesions was demonstrated by infusion of colloidal carbon. In one strain, A, an estimate of the proportion of nonperfused lung was made on distressed late-stage mice. Almost 50% of lung acini were nonfunctional as a result of nonperfusion, and an additional 9% of acini were nonfunctional due to lesions obstructing ventilation. It is suggested that nonperfusion of apparently normal lung acini is a major factor in late-phase deaths in those mouse strains which show little or no fibrosis.

  2. Phenotypic integration of skeletal traits during growth buffers genetic variants affecting the slenderness of femora in inbred mouse strains

    PubMed Central

    Jepsen, Karl J.; Hu, Bin; Tommasini, Steven M.; Courtland, Hayden-William; Price, Christopher; Cordova, Matthew; Nadeau, Joseph H.

    2009-01-01

    Compensatory interactions among adult skeletal traits are critical for establishing strength but complicate the search for fracture susceptibility genes by allowing many genetic variants to exist in a population without loss of function. A better understanding of how these interactions arise during growth will provide new insight into genotype-phenotype relationships and the biological controls that establish skeletal strength. We tested the hypothesis that genetic variants affecting growth in width relative to growth in length (slenderness) are coordinated with movement of the inner bone surface and matrix mineralization to match stiffness with weight-bearing loads during postnatal growth. Midshaft femoral morphology and tissue-mineral density were quantified at ages of 1 day and at 4, 8, and 16 weeks for a panel of 20 female AXB/BXA recombinant inbred mouse strains. Path Analyses revealed significant compensatory interactions among outer-surface expansion rate, inner-surface expansion rate, and tissue-mineral density during postnatal growth, indicating that genetic variants affecting bone slenderness were buffered mechanically by the precise regulation of bone surface movements and matrix mineralization. Importantly, the covariation between morphology and mineralization resulted from a heritable constraint limiting the amount of tissue that could be used to construct a functional femur. The functional interactions during growth explained 56-99% of the variability in adult traits and mechanical properties. These functional interactions provide quantitative expectations of how genetic or environmental variants affecting one trait should be compensated by changes in other traits. Variants that impair this process or that cannot be fully compensated are expected to alter skeletal growth leading to underdesigned (weak) or overdesigned (bulky) structures. PMID:19082857

  3. Mouse model of congenital infection with a non-virulent Toxoplasma gondii strain: Vertical transmission, "sterile" fetal damage, or both?

    PubMed

    Vargas-Villavicencio, J A; Cedillo-Peláez, C; Rico-Torres, C P; Besné-Mérida, A; García-Vázquez, F; Saldaña, J I; Correa, D

    2016-07-01

    Congenital transmission of Toxoplasma gondii may occur if the mother gets infected for the first time while pregnant. The risk of mother-to-child transmission depends on the gestation trimester at infection, being lowest in the first and highest in the last. Conversely, fetal damage is frequent and more severe at the beginning of pregnancy. The objective of this study was to evaluate congenital transmission and pathological aspects in the placenta and the fetus using a mouse model of congenital infection of the second gestation third. Forty-five female BALB/c mice were infected intravenously with 2.5-10.0 × 10(6) tachyzoites of the ME49 strain at middle gestation. Samples of maternal spleen and fetal/placental units were taken 72 h later. We determined parasite load and vertical transmission by qPCR, as well as damage macroscopically and by histopathology. With the lowest dose, 18% of the fetuses were infected. Also, 40% of fetuses/litter were altered, while this value was 10% in the control group (P < 0.05). These results are similar to those described in humans in terms of vertical transmission and fetal damage during the second third of gestation. The maternal spleen had 10-1000 times more tachyzoites than the placenta, and the later retained 90-99% of the parasites that could reach the fetus. Nevertheless, we found resorptions, abortions or fetal tissue damage in the presence but also in the absence of parasites. Our data indicate a strong protective effect of maternal organs and the placenta against fetal infection, but extensive damage of the later may led to resorption or abortion without vertical transmission. PMID:27068784

  4. Mouse cytokine profile skewed towards Th2 in pregnancy during infection with Brucella abortus S19 strain.

    PubMed

    Wamonje, Francis O; Waihenya, Rebecca K; Ng'ang'a, Zipporah; Ngeranwa, Joseph N

    2011-04-01

    The two classes of cytokines Th1 and Th2 determine the type of immune response elicited. The Th2 immune response is associated with successful pregnancy. Brucellosis is an intracellular bacterium that elicits the Th1 response and is known to cause spontaneous abortion in mammalian species. This study sought to determine if Brucella infection causes spontaneous abortion by causing the circulating cytokine profile be Th1 dominant during pregnancy. Forty-eight Swiss white mice were used in this murine model and the S19 strain of Brucella abortus was used in as the infective agent. Pregnant mice in the test group were injected intraperitoneally with 10(5-8) CFU of Brucella and cytokine profile evaluated over the three trimesters of pregnancy. Pregnant mice in the control group were left to go through normal pregnancy and their cytokine profile evaluated over the three trimesters of pregnancy. Cytokines in serum samples were analyzed by Cytometric Bead Array. The data was analyzed using the Paired T- test and p < 0.05 was considered significant. IFN-γ and TNF-α represented the Th1 cytokines while IL-4 and IL-5 represented the Th2 cytokines. None of the mice in the test group had spontaneous abortion. IFN-γ and TNF-α had no significant differences between cytokine levels for infected and uninfected groups in all 3 trimesters of pregnancy. IL-4 levels had significant differences in all three trimesters of pregnancy (t = 13, P = 0.036, 0.0071 and 0.0277). IL-5 levels had significant differences second trimester (t = 14, P = 0.0075). The cytokine profile was robustly Th2. In conclusion, Brucella abortus cannot cause spontaneous abortion by altering the mouse cytokine profile towards Th1 in pregnancy. Elevated IL-4 levels with corresponding suppression of IFN-γ can be used as a marker for successful pregnancy in Brucellosis. PMID:25566611

  5. IDENTIFICATION OF STEREOCHEMICAL CONFIGURATIONS OF CYCLOPENTA[CD]PYRENE-DNA ADDUCTS IN STRAIN A/J MOUSE LUNG AND C3H10T1/2CL8 CELLS

    EPA Science Inventory

    Identification of Sterochemical Configurations of Cyclopent A[cd]Pyrene DNA Adducts in Strain A/J Mouse Lung and C3H10T1/2CL8 Cells.

    Four major and several minor DNA adducts were resolved by 32P-postlabeling analysis of DNA from strain A/J mouse lung and C3H10T1/2CL8 (C3H...

  6. The t(14,15) in Mouse Strain CBA/CaH-T(14;15)6Ca/J Causes a Break in the ADAMTS12 Gene

    PubMed Central

    Acar-Perk, Bengi; Bräutigam, Karen; Grunewald, Regina; Schmutzler, Andreas; Schem, Christian; Arnold, Norbert K; Jonat, Walter; Weimer, Jörg

    2010-01-01

    The mouse strain CBA/CaH-T(14;15)6Ca/J carries a homozygous balanced reciprocal translocation between mouse chromosomes 14 and 15, but the break points of this translocation have not previously been examined in detail. Using fluorescent in situ hybridization, we assigned the break point in 14qE3 to a 200-kb region devoid of any known gene. We similarly defined the break point in 15qA1 to a 27-kb region containing involving ADAMTS12. The chromosomal break likely is between exons 2 and 3 of ADAMTS12. This gene encodes a disintegrin and metalloproteinase with thrombospondin motifs, and this product plays crucial roles in both vascularization and cancer progression and has been implicated in the development of arthritis. The CBA/CaH-T(14;15)6Ca/J mouse strain likely is a suitable model for further examination of the influences of defective ADAMTS12 in various pathologic processes. PMID:20412686

  7. Genetic variation responsible for mouse strain differences in integrin {alpha}{sub 2} expression is associated with altered platelet responses to collagen

    SciTech Connect

    Li, Tong-Tong; Larrucea, Susana; Souza, Shiloe; Leal, Suzanne M.; Lopez, Jose A.; Rubin, Edward M.; Nieswandt, Bernhard; Bray, Paul F.

    2003-11-01

    Formation of a thrombus at the site of an injured vessel requires the coordinated action of critical platelet plasma membrane adhesion molecules. The most important initial contact of platelets with the exposed endothelial collagen and von Willebrand factor (VWF) involves the binding of glycoprotein (GP) Ib{alpha} to immobilized VWF. The VWF-GPIb{alpha} interaction is ''fast-on'' and relatively ''fast-off,'' and results in a rolling of platelets along the exposed subendothelium. This slowing of the platelets allows binding of the activating collagen-receptor, GPVI, to its ligand, resulting in activation of platelet integrins and subsequent firm adhesion, where the reactions between receptor and ligand are relatively ''slow-on'' but irreversible. The binding of integrin {alpha}{sub 2} {beta}{sub 1} underlying firm adhesion. Intracellular signaling between and through these adhesive receptors plays a crucial role in platelet adhesion and aggregation. The importance of the GPIb-IX-V and {alpha}{sub IIb} {beta}{sub 3} in normal hemostasis is under scored by the bleeding diatheses that have been reported in patients with quantitative or qualitative deficiencies of the genes that encode them. Mouse models are now commonplace for studying hemostasis and thrombosis, and important insights pertaining to the major platelet adhesive receptors have been gleaned from mouse studies involving targeted disruptions of the genes for GPIb{alpha}, GPVI, and integrin chains 2,9,10 1,4 IIb 11 and 3.12 A variety of different mouse strains have been used to assess hemostasis. For example, the FVB strain is typically used for transgenic experiments, the 129/Sv strain is used to derive embryonic stem (ES) cells, and the C57 strain is used for uniform background breeding studies. Different strains may exhibit different levels of gene expression, a feature that has been used to elucidate crucial gene regions regulating transcription. We and others have previously studied how genetic changes

  8. Response to ethanol induced ataxia between C57BL/6J and 129X1/SvJ mouse strains using a treadmill based assay

    PubMed Central

    Hansen, Stephen T.; Pulst, Stefan M.

    2016-01-01

    More sensitive assays of mouse motor ataxia may provide a better understanding of the pathological profile. Treadmill gait analysis using ventral imaging allows for unhindered access to the ambulating mouse. In contrast to genetic mutations or exogenous brain injury, ethanol (EtOH) allows for the detection of dose dependent changes in motor behavior, which can be used to assess an assay’s detection sensitivity. EtOH induced ataxia was assessed in C57BL/6J (B6) and 129X1/SvJ (129) mice using the DigiGait imaging system. Gait was analyzed across EtOH dosage (1.75, 2.25 and 2.75 g/kg) in each strain using a linear mixed effects model. Overall, 129 mice displayed greater susceptibility to EtOH ataxia than their B6 counterparts. In both strains, hind paws exhibited greater sensitivity to EtOH dosage than fore paws. Across most variables analyzed, only a modest EtOH-induced change in motor behavior was observed in each strain with the 1.75g/kg EtOH doses failing to elicit significant change. These data indicate the ability to detect motor differences between strains, yet only moderate ability to detect change across EtOH dosage using the automated treadmill. Rotarod assays, however, were able to detect motor impairment at lower doses of EtOH. The significant, but opposite changes in paw placement with increasing EtOH doses highlight strain-specific differences in biophysical adaptations in response to acute EtOH intoxication. PMID:23103202

  9. A Mouse Strain Less Responsive to Dioxin-Induced Prostaglandin E2 Synthesis Is Resistant to the Onset of Neonatal Hydronephrosis

    PubMed Central

    Kawaguchi, Tatsuya; Ohsako, Seiichiroh; Tohyama, Chiharu

    2014-01-01

    Dioxin is a ubiquitous environmental pollutant that induces toxicity when bound to the aryl hydrocarbon receptor (AhR). Significant differences in susceptibility of mouse strains to dioxin toxicity are largely accounted for by the dissociation constant of binding to dioxins of AhR subtypes encoded by different alleles. We showed that cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1), components of a prostanoid synthesis pathway, play essential roles in the onset of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced hydronephrosis of neonatal mice. Although C57BL/6J and BALB/cA mice harbor AhR receptors highly responsive to TCDD, they were found by chance to differ significantly in the incidence of TCDD-induced hydronephrosis. Therefore, the goal of the present study was to determine the molecular basis of this difference in susceptibility to TCDD toxicity. For this purpose, we administered C57BL/6J and BALB/cA dams’ TCDD at an oral dose of 15 or 80 μg/kg on postnatal day (PND) 1 to expose pups to TCDD via lactation, and the pups’ kidneys were collected on PND 7. The incidence of hydronephrosis in C57BL/6J pups (64%) was greater than in BALB/cA pups (0%, p < 0.05), despite similarly increased levels of COX-2 mRNA. The incidence of hydronephrosis in these mouse strains paralleled the levels of renal mPGES-1 mRNA and early growth response 1 (Egr-1) that modulates mPGES-1 gene expression, as well as PGE2 concentrations in urine. Although these mouse strains possess AhR alleles tightly bound to TCDD, their difference in incidence and severity of hydronephrosis can be explained, in part, by differences in the expression of mPGES-1 and Egr-1. PMID:25015655

  10. D2-like dopamine receptor mediation of social-emotional reactivity in a mouse model of anxiety: strain and experience effects.

    PubMed

    Gendreau, P L; Petitto, J M; Gariépy, J L; Lewis, M H

    1998-03-01

    We examined the effects of the D2-like dopamine receptor agonist quinpirole on social-emotional reactivity in two inbred mouse strains. An important objective of this study was to determine whether these effects could be modulated by differential housing conditions (i.e., isolation versus group housing). Moreover, as motor activity is an important control for the assessment of drug effects on emotional behavior, the effects of quinpirole were tested in two inbred mouse strains (A/J and C57BL/6J) low and high in motor activity, respectively. Levels of emotional reactivity were assessed in response to mild social stimulation provided by a nonaggressive conspecific. Quinpirole increased stationary forms of reactivity (i.e., startle, kicking, defensive posture, vocalization) in both isolated and group-housed A/J mice. This effect was more pronounced and observed at lower doses in isolated than in group-housed A/J mice. Quinpirole also induced jump behavior in isolated but not group-housed A/J mice. The shift to the left in the dose-response curve of quinpirole in isolated A/J mice indicated that D2-like dopamine receptor functions can be altered by social experience. Quinpirole only marginally increased stationary and locomotor reactivity (i.e., jump) in isolated C57BL/6J mice, whereas it markedly reduced motor activity in group-housed mice of this strain. The investigation of emotional reactivity within a social context and using strains that differ in motor activity permitted the effects of drugs on emotional reactivity to be dissociated from the effects on motor activity. Given that social-emotional reactivity was elicited by what typically should have been mild and nonthreatening stimuli, this model may be highly relevant to understanding the neurobiology of anxiety. Finally, these data support an important role for dopamine in the mediation of social-emotional reactivity. PMID:9471118

  11. Genetic Dissection of Quantitative Trait Loci for Hemostasis and Thrombosis on Mouse Chromosomes 11 and 5 Using Congenic and Subcongenic Strains

    PubMed Central

    Hoover-Plow, Jane; Sa, Qila; Huang, Menggui; Grondolsky, Jessica

    2013-01-01

    Susceptibility to thrombosis varies in human populations as well as many inbred mouse strains. Only a small portion of this variation has been identified, suggesting that there are unknown modifier genes. The objective of this study was to narrow the quantitative trait locus (QTL) intervals previously identified for hemostasis and thrombosis on mouse distal chromosome 11 (Hmtb6) and on chromosome 5 (Hmtb4 and Hmtb5). In a tail bleeding/rebleeding assay, a reporter assay for hemostasis and thrombosis, subcongenic strain (6A-2) had longer clot stability time than did C57BL/6J (B6) mice but a similar time to the B6-Chr11A/J consomic mice, confirming the Hmtb6 phenotype. Six congenic and subcongenic strains were constructed for chromosome 5, and the congenic strain, 2A-1, containing the shortest A/J interval (16.6 cM, 26.6 Mbp) in the Hmtb4 region, had prolonged clot stability time compared to B6 mice. In the 3A-2 and CSS-5 mice bleeding time was shorter than for B6, mice confirming the Hmtb5 QTL. An increase in bleeding time was identified in another congenic strain (3A-1) with A/J interval (24.8 cM, 32.9 Mbp) in the proximal region of chromosome 5, confirming a QTL for bleeding previously mapped to that region and designated as Hmtb10. The subcongenic strain 4A-2 with the A/J fragment in the proximal region had a long occlusion time of the carotid artery after ferric chloride injury and reduced dilation after injury to the abdominal aorta compared to B6 mice, suggesting an additional locus in the proximal region, which was designated Hmtb11 (5 cM, 21.4 Mbp). CSS-17 mice crossed with congenic strains, 3A-1 and 3A-2, modified tail bleeding. Using congenic and subcongenic analysis, candidate genes previously identified and novel genes were identified as modifiers of hemostasis and thrombosis in each of the loci Hmtb6, Hmtb4, Hmtb10, and Hmtb11. PMID:24147020

  12. Transcriptome Analysis of Genes Regulated by Cholesterol Loading in Two Strains of Mouse Macrophages Associates Lysosome Pathway and ER Stress Response with Atherosclerosis Susceptibility

    PubMed Central

    Robinet, Peggy; Smith, Jonathan D.

    2013-01-01

    Cholesterol loaded macrophages in the arterial intima are the earliest histological evidence of atherosclerosis. Studies of mouse models of atherosclerosis have shown that the strain background can have a significant effect on lesion development. We have previously shown that DBA/2 ApoE−/− mice have aortic root lesions 10-fold larger than AKR ApoE−/−mice. The current study analyzes the response to cholesterol loading of macrophages from these two strains. Macrophages from the atherosclerosis susceptible DBA/2 strain had significantly higher levels of total and esterified cholesterol compared to atherosclerosis resistant AKR macrophages, while free cholesterol levels were higher in AKR cells. Gene expression profiles were obtained and data were analyzed for strain, cholesterol loading, and strain-cholesterol loading interaction effects by a fitted linear model. Pathway and transcriptional motif enrichment were identified by gene set enrichment analysis. In addition to observed strain differences in basal gene expression, we identified many transcripts whose expression was significantly altered in response to cholesterol loading, including P2ry13 and P2ry14, Trib3, Hyal1, Vegfa, Ccr5, Ly6a, and Ifit3. Eight pathways were significantly enriched in transcripts regulated by cholesterol loading, among which the lysosome and cytokine-cytokine receptor interaction pathways had the highest number of significantly regulated transcripts. Of the differentially regulated transcripts with a strain-cholesterol loading interaction effect, we identified three genes known to participate in the endoplasmic reticulum (ER) stress response, Ddit3, Trib3 and Atf4. These three transcripts were highly up-regulated by cholesterol in AKR and either down-regulated or unchanged in loaded DBA/2 macrophages, thus associating a robust ER stress response with atherosclerosis resistance. We identified significant transcripts with strain, loading, or strain-loading interaction effect that

  13. Transcriptome analysis of genes regulated by cholesterol loading in two strains of mouse macrophages associates lysosome pathway and ER stress response with atherosclerosis susceptibility.

    PubMed

    Berisha, Stela Z; Hsu, Jeffrey; Robinet, Peggy; Smith, Jonathan D

    2013-01-01

    Cholesterol loaded macrophages in the arterial intima are the earliest histological evidence of atherosclerosis. Studies of mouse models of atherosclerosis have shown that the strain background can have a significant effect on lesion development. We have previously shown that DBA/2 ApoE(-/-) mice have aortic root lesions 10-fold larger than AKR ApoE(-/-) mice. The current study analyzes the response to cholesterol loading of macrophages from these two strains. Macrophages from the atherosclerosis susceptible DBA/2 strain had significantly higher levels of total and esterified cholesterol compared to atherosclerosis resistant AKR macrophages, while free cholesterol levels were higher in AKR cells. Gene expression profiles were obtained and data were analyzed for strain, cholesterol loading, and strain-cholesterol loading interaction effects by a fitted linear model. Pathway and transcriptional motif enrichment were identified by gene set enrichment analysis. In addition to observed strain differences in basal gene expression, we identified many transcripts whose expression was significantly altered in response to cholesterol loading, including P2ry13 and P2ry14, Trib3, Hyal1, Vegfa, Ccr5, Ly6a, and Ifit3. Eight pathways were significantly enriched in transcripts regulated by cholesterol loading, among which the lysosome and cytokine-cytokine receptor interaction pathways had the highest number of significantly regulated transcripts. Of the differentially regulated transcripts with a strain-cholesterol loading interaction effect, we identified three genes known to participate in the endoplasmic reticulum (ER) stress response, Ddit3, Trib3 and Atf4. These three transcripts were highly up-regulated by cholesterol in AKR and either down-regulated or unchanged in loaded DBA/2 macrophages, thus associating a robust ER stress response with atherosclerosis resistance. We identified significant transcripts with strain, loading, or strain-loading interaction effect that

  14. Production of a mouse strain with impaired glucose tolerance by systemic heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes model

    PubMed Central

    SAITO, Mikako; KANEDA, Asako; SUGIYAMA, Tae; IIDA, Ryousuke; OTOKUNI, Keiko; KABURAGI, Misako; MATSUOKA, Hideaki

    2015-01-01

    Exon II of glucokinase (Gk) was deleted to produce a systemic heterozygous Gk knockout (Gk+/−) mouse. The relative expression levels of Gk in the heart, lung, liver, stomach, and pancreas in Gk+/− mice ranged from 0.41–0.68 versus that in wild (Gk+/+) mice. On the other hand, its expression levels in the brain, adipose tissue, and muscle ranged from 0.95–1.03, and its expression levels in the spleen and kidney were nearly zero. Gk knockout caused no remarkable off-target effect on the expression of 7 diabetes causing genes (Shp, Hnf1a, Hnf1b, Irs1, Irs2, Kir6.2, and Pdx1) in 10 organs. The glucose tolerance test was conducted to determine the blood glucose concentrations just after fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). The FBG-GTT2h plots obtained with the wild strain fed the control diet (CD), Gk+/− strain fed the CD, and Gk+/− strain fed the HFD were distributed in separate areas in the FBG-GTT2h diagram. The respective areas could be defined as the normal state, prediabetes state, and diabetes state, respectively. Based on the results, the criteria for prediabetes could be defined for the Gk+/− strain developed in this study. PMID:25765873

  15. The formation of titan cells in Cryptococcus neoformans depends on the mouse strain and correlates with induction of Th2-type responses.

    PubMed

    García-Barbazán, Irene; Trevijano-Contador, Nuria; Rueda, Cristina; de Andrés, Belén; Pérez-Tavárez, Raquel; Herrero-Fernández, Inés; Gaspar, María Luisa; Zaragoza, Oscar

    2016-01-01

    Cryptococcus neoformans is a pathogenic yeast that can form titan cells in the lungs, which are fungal cells of abnormal enlarged size. Little is known about the factors that trigger titan cells. In particular, it is not known how the host environment influences this transition. In this work, we describe the formation of titan cells in two mouse strains, CD1 and C57BL/6J. We found that the proportion of C. neoformans titan cells was significantly higher in C57BL/6J mice than in CD1. This higher proportion of titan cells was associated with a higher dissemination of the yeasts to the brain. Histology sections demonstrated eosinophilia in infected animals, although it was significantly lower in the CD1 mice which presented infiltration of lymphocytes. Both mouse strains presented infiltration of granulocytes, but the amount of eosinophils was higher in C57BL/6J. CD1 mice showed a significant accumulation of IFN-γ, TNF-α and IL17, while C57BL/BL mice had an increase in the anti-inflammatory cytokine IL-4. IgM antibodies to the polysaccharide capsule and total IgE were more abundant in the sera from C57BL/6J, confirming that these animals present a Th2-type response. We conclude that titan cell formation in C. neoformans depends, not only on microbe factors, but also on the host environment. PMID:26243235

  16. Divergent compensatory responses to high-fat diet between C57BL6/J and C57BLKS/J inbred mouse strains

    PubMed Central

    Sims, Emily K.; Hatanaka, Masayuki; Morris, David L.; Tersey, Sarah A.; Kono, Tatsuyoshi; Chaudry, Zunaira Z.; Day, Kathleen H.; Moss, Dan R.; Stull, Natalie D.; Mirmira, Raghavendra G.

    2013-01-01

    Impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) are polygenic disorders with complex pathophysiologies; recapitulating them with mouse models is challenging. Despite 70% genetic homology, C57BL/6J (BL6) and C57BLKS/J (BLKS) inbred mouse strains differ in response to diet- and genetic-induced obesity. We hypothesized these differences would yield insight into IGT and T2DM susceptibility and response to pharmacological therapies. To this end, male 8-wk-old BL6 and BLKS mice were fed normal chow (18% kcal from fat), high-fat diet (HFD; 42% kcal from fat), or HFD supplemented with the PPARγ agonist pioglitazone (PIO; 140 mg PIO/kg diet) for 16 wk. Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were undertaken. BL6 mice gained weight and adiposity in response to HFD, leading to peripheral insulin resistance that was met with increased β-cell proliferation and insulin production. By contrast, BLKS mice responded to HFD by restricting food intake and increasing activity. These behavioral responses limited weight gain and protected against HFD-induced glucose intolerance, which in this strain was primarily due to β-cell dysfunction. PIO treatment did not affect HFD-induced weight gain in BL6 mice, and decreased visceral fat mass, whereas in BLKS mice PIO increased total fat mass without improving visceral fat mass. Differences in these responses to HFD and effects of PIO reflect divergent human responses to a Western lifestyle and underscore the careful consideration needed when choosing mouse models of diet-induced obesity and diabetes treatment. PMID:24169046

  17. Obesity reduces left ventricular strains, torsion, and synchrony in mouse models: a cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance study

    PubMed Central

    2013-01-01

    Background Obesity affects a third of adults in the US and results in an increased risk of cardiovascular mortality. While the mechanisms underlying this increased risk are not well understood, animal models of obesity have shown direct effects on the heart such as steatosis and fibrosis, which may affect cardiac function. However, the effect of obesity on cardiac function in animal models is not well-defined. We hypothesized that diet-induced obesity in mice reduces strain, torsion, and synchrony in the left ventricle (LV). Methods Ten 12-week-old C57BL/6 J mice were randomized to a high-fat or low-fat diet. After 5 months on the diet, mice were imaged with a 7 T ClinScan using a cine DENSE protocol. Three short-axis and two long-axis slices were acquired for quantification of strains, torsion and synchrony in the left ventricle. Results Left ventricular mass was increased by 15% (p = 0.032) with no change in volumes or ejection fraction. Subepicardial strain was lower in the obese mice with a 40% reduction in circumferential strain (p = 0.008) a 53% reduction in radial strain (p = 0.032) and a trend towards a 19% reduction in longitudinal strain (p = 0.056). By contrast, subendocardial strain was modestly reduced in the obese mice in the circumferential direction by 12% (p = 0.028), and no different in the radial (p = 0.690) or longitudinal (p = 0.602) directions. Peak torsion was reduced by 34% (p = 0.028). Synchrony of contraction was also reduced (p = 0.032) with a time delay in the septal-to-lateral direction. Conclusions Diet-induced obesity reduces left ventricular strains and torsion in mice. Reductions in cardiac strain are mostly limited to the subepicardium, with relative preservation of function in the subendocardium. Diet-induced obesity also leads to reduced synchrony of contraction and hypertrophy in mouse models. PMID:24380567

  18. Sequential Application of Glass Coverslips to Assess the Compressive Stiffness of the Mouse Lens: Strain and Morphometric Analyses.

    PubMed

    Cheng, Catherine; Gokhin, David S; Nowak, Roberta B; Fowler, Velia M

    2016-01-01

    The eye lens is a transparent organ that refracts and focuses light to form a clear image on the retina. In humans, ciliary muscles contract to deform the lens, leading to an increase in the lens' optical power to focus on nearby objects, a process known as accommodation. Age-related changes in lens stiffness have been linked to presbyopia, a reduction in the lens' ability to accommodate, and, by extension, the need for reading glasses. Even though mouse lenses do not accommodate or develop presbyopia, mouse models can provide an invaluable genetic tool for understanding lens pathologies, and the accelerated aging observed in mice enables the study of age-related changes in the lens. This protocol demonstrates a simple, precise, and cost-effective method for determining mouse lens stiffness, using glass coverslips to apply sequentially increasing compressive loads onto the lens. Representative data confirm that mouse lenses become stiffer with age, like human lenses. This method is highly reproducible and can potentially be scaled up to mechanically test lenses from larger animals. PMID:27166880

  19. Design of a new stretching apparatus and the effects of cyclic strain and substratum on mouse lung epithelial-12 cells.

    PubMed

    Arold, Stephen P; Wong, Joyce Y; Suki, Bela

    2007-07-01

    The pulmonary epithelium is exposed to mechanical strains during normal breathing or mechanical ventilation. While important for the regulation of cellular processes, excessive strains damage epithelial cells. To investigate the effects of strain on the epithelium, we developed a stretching device to apply equi-biaxial strains to cells cultured on elastic membranes. Following device validation, we exposed a murine epithelial cell line (MLE-12) to 30 min of cyclic stretch with 0, 25, 50, 75 and 100% change in surface area on pronectin or type I collagen coated membranes. Following stretch, we assessed cell viability using fluorescent immunocytochemisty and surfactant secretion using [(3)H] labeled phosphatidylcholine (PC). Cell injury increased with increasing strain with cells on pronectin showing more injury than on type I collagen. Stretching had no effect on surfactant secretion on either substratum suggesting MLE-12 cells are a poor model for stretch-induced surfactant secretion. The cells grown on pronectin, however, demonstrated a 3-fold increase in surfactant secretion compared to those grown on type I collagen at all strains. This suggests that, while this cell line does not demonstrate stretch-induced surfactant secretion, the underlying extracellular matrix plays a crucial factor in both cell death and signal transduction in response to strain. PMID:17578668

  20. Nutritional basis for colonization resistance by human commensal Escherichia coli strains HS and Nissle 1917 against E. coli O157:H7 in the mouse intestine.

    PubMed

    Maltby, Rosalie; Leatham-Jensen, Mary P; Gibson, Terri; Cohen, Paul S; Conway, Tyrrell

    2013-01-01

    Escherichia coli is a single species consisting of many biotypes, some of which are commensal colonizers of mammals and others that cause disease. Humans are colonized on average with five commensal biotypes, and it is widely thought that the commensals serve as a barrier to infection by pathogens. Previous studies showed that a combination of three pre-colonized commensal E. coli strains prevents colonization of E. coli O157:H7 in a mouse model (Leatham, et al., 2010, Infect Immun 77: 2876-7886). The commensal biotypes included E. coli HS, which is known to successfully colonize humans at high doses with no adverse effects, and E. coli Nissle 1917, a human commensal strain that is used in Europe as a preventative of traveler's diarrhea. We hypothesized that commensal biotypes could exert colonization resistance by consuming nutrients needed by E. coli O157:H7 to colonize, thus preventing this first step in infection. Here we report that to colonize streptomycin-treated mice E. coli HS consumes six of the twelve sugars tested and E. coli Nissle 1917 uses a complementary yet divergent set of seven sugars to colonize, thus establishing a nutritional basis for the ability of E. coli HS and Nissle 1917 to occupy distinct niches in the mouse intestine. Together these two commensals use the five sugars previously determined to be most important for colonization of E. coli EDL933, an O157:H7 strain. As predicted, the two commensals prevented E. coli EDL933 colonization. The results support a model in which invading pathogenic E. coli must compete with the gut microbiota to obtain the nutrients needed to colonize and establish infection; accordingly, the outcome of the challenge is determined by the aggregate capacity of the native microbiota to consume the nutrients required by the pathogen. PMID:23349773

  1. Nutritional Basis for Colonization Resistance by Human Commensal Escherichia coli Strains HS and Nissle 1917 against E. coli O157:H7 in the Mouse Intestine

    PubMed Central

    Maltby, Rosalie; Leatham-Jensen, Mary P.; Gibson, Terri; Cohen, Paul S.; Conway, Tyrrell

    2013-01-01

    Escherichia coli is a single species consisting of many biotypes, some of which are commensal colonizers of mammals and others that cause disease. Humans are colonized on average with five commensal biotypes, and it is widely thought that the commensals serve as a barrier to infection by pathogens. Previous studies showed that a combination of three pre-colonized commensal E. coli strains prevents colonization of E. coli O157:H7 in a mouse model (Leatham, et al., 2010, Infect Immun 77: 2876–7886). The commensal biotypes included E. coli HS, which is known to successfully colonize humans at high doses with no adverse effects, and E. coli Nissle 1917, a human commensal strain that is used in Europe as a preventative of traveler's diarrhea. We hypothesized that commensal biotypes could exert colonization resistance by consuming nutrients needed by E. coli O157:H7 to colonize, thus preventing this first step in infection. Here we report that to colonize streptomycin-treated mice E. coli HS consumes six of the twelve sugars tested and E. coli Nissle 1917 uses a complementary yet divergent set of seven sugars to colonize, thus establishing a nutritional basis for the ability of E. coli HS and Nissle 1917 to occupy distinct niches in the mouse intestine. Together these two commensals use the five sugars previously determined to be most important for colonization of E. coli EDL933, an O157:H7 strain. As predicted, the two commensals prevented E. coli EDL933 colonization. The results support a model in which invading pathogenic E. coli must compete with the gut microbiota to obtain the nutrients needed to colonize and establish infection; accordingly, the outcome of the challenge is determined by the aggregate capacity of the native microbiota to consume the nutrients required by the pathogen. PMID:23349773

  2. Effect of Acute Swim Stress on Plasma Corticosterone and Brain Monoamine Levels in Bidirectionally Selected DxH Recombinant Inbred Mouse Strains Differing in Fear Recall and Extinction

    PubMed Central

    Browne, Caroline A.; Hanke, Joachim; Rose, Claudia; Walsh, Irene; Foley, Tara; Clarke, Gerard; Schwegler, Herbert; Cryan, John F.; Yilmazer-Hanke, Deniz

    2015-01-01

    Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus, and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 minutes after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or posttraumatic stress disorder. PMID:25117886

  3. Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction.

    PubMed

    Browne, Caroline A; Hanke, Joachim; Rose, Claudia; Walsh, Irene; Foley, Tara; Clarke, Gerard; Schwegler, Herbert; Cryan, John F; Yilmazer-Hanke, Deniz

    2014-12-01

    Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites 3,4-dihydroxyphenyacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 min after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or post-traumatic stress disorder. PMID:25117886

  4. Immune Status, Strain Background, and Anatomic Site of Inoculation Affect Mouse Papillomavirus (MmuPV1) Induction of Exophytic Papillomas or Endophytic Trichoblastomas

    PubMed Central

    Sundberg, John P.; Proctor, Mary; Ingle, Arvind; Silva, Kathleen A.; Dadras, Soheil S.; Jenson, A. Bennett; Ghim, Shin-je

    2014-01-01

    Papillomaviruses (PVs) induce papillomas, premalignant lesions, and carcinomas in a wide variety of species. PVs are classified first based on their host and tissue tropism and then their genomic diversities. A laboratory mouse papillomavirus, MmuPV1 (formerly MusPV), was horizontally transmitted within an inbred colony of NMRI-Foxn1nu/Foxn1nu (nude; T cell deficient) mice of an unknown period of time. A ground-up, filtered papilloma inoculum was not capable of infecting C57BL/6J wild-type mice; however, immunocompetent, alopecic, S/RV/Cri-ba/ba (bare) mice developed small papillomas at injection sites that regressed. NMRI-Foxn1nu and B6.Cg-Foxn1nu, but not NU/J-Foxn1nu, mice were susceptible to MmuPV1 infection. B6 congenic strains, but not other congenic strains carrying the same allelic mutations, lacking B- and T-cells, but not B-cells alone, were susceptible to infection, indicating that mouse strain and T-cell deficiency are critical to tumor formation. Lesions initially observed were exophytic papillomas around the muzzle, exophytic papillomas on the tail, and condylomas of the vaginal lining which could be induced by separate scarification or simultaneous scarification of MmuPV1 at all four sites. On the dorsal skin, locally invasive, poorly differentiated tumors developed with features similar to human trichoblastomas. Transcriptome analysis revealed significant differences between the normal skin in these anatomic sites and in papillomas versus trichoblastomas. The primarily dysregulated genes involved molecular pathways associated with cancer, cellular development, cellular growth and proliferation, cell morphology, and connective tissue development and function. Although trichoepitheliomas are benign, aggressive tumors, few of the genes commonly associated with basal cell carcinoma or squamous cells carcinoma were highly dysregulated. PMID:25474466

  5. Mouse strain-dependent variation in the course and outcome of chlamydial genital tract infection is associated with differences in host response.

    PubMed Central

    Darville, T; Andrews, C W; Laffoon, K K; Shymasani, W; Kishen, L R; Rank, R G

    1997-01-01

    Whether there is a pathogenic or protective outcome to chlamydial infection may be defined by the host response. We infected C57BL/6 (C57) and C3H/HeN (C3H) mice with the human biovar of Chlamydia trachomatis, serovar E, and, in select experiments, with the mouse pneumonitis agent of C. trachomatis (MoPn). We compared the courses of infection, histopathology, and host responses that resulted from these infections. The duration of infection with either chlamydial biovar was significantly increased in the C3H strain of mice. The intensity of infection was examined in mice infected with serovar E, and it was significantly increased in the C3H strain. Histopathology revealed the incidence of severe hydrosalpinx to be significantly greater in C3H mice than in C57 mice. In contrast, severe distention of the uterine horns was observed in all infected C57 mice compared to none of the C3H mice infected with serovar E and only 25% of those infected with MoPn. Acute inflammation was significantly increased in the uterine horns of C57 mice compared to that of C3H mice. Examination of antigen-specific responses revealed qualitatively similar responses in the two strains. Determination of gamma interferon- versus interleukin 4- producing cells revealed the predominance of a Th1 response in both strains. Serum enzyme-linked immunosorbent assays for immunoglobulin G1 (IgG1) and IgG2a revealed a predominance of IgG2a antibody in both strains, although the levels of antibody were significantly greater in C3H mice. Lymphocyte proliferation studies revealed increased proliferation in the iliac nodes of both strains at 1 to 3 weeks after infection. Because of the early eradication of infection observed in the C57 strain, we explored the relative production of tumor necrosis factor alpha (TNF-alpha) in the two strains. TNF-alpha levels were significantly increased in the genital tract secretions of C57 mice compared to that of C3H mice during the first week of infection. Increased TNF

  6. Colonization of the streptomycin-treated mouse large intestine by a human fecal Escherichia coli strain: role of growth in mucus.

    PubMed Central

    Wadolkowski, E A; Laux, D C; Cohen, P S

    1988-01-01

    The relative colonizing abilities of Escherichia coli F-18, isolated from the feces of a healthy human, and E. coli F-18col-, a strain derived from it which does not make the E. coli F-18 colicin, were studied. In a previous report, it was shown that when each strain was fed individually to streptomycin-treated mice, at approximately 10(10) CFU per mouse, each colonized the large intestine at between 10(7) and 10(8) CFU/g of feces indefinitely. However, when simultaneously fed to mice, although E. coli F-18 colonized at about 10(8) CFU/g of feces, E. coli F-18col- dropped to a level of 10(3) CFU/g of feces within 3 to 5 days. In the present investigation, we show that when given enough time to establish a state of colonization, E. coli F-18col- persists in feces in high numbers despite subsequent challenge by E. coli F-18. Therefore, a major defect in the ability of E. coli F-18col- to colonize in the presence of E. coli F-18 appears to be in initiating that state. In addition, when mucus was scraped from the cecal wall and, without further treatment, was inoculated with E. coli F-18 or F-18col-, both strains grew well. However, when cecal mucus was inoculated with both strains simultaneously, E. coli F-18 grew far more rapidly than E. coli F-18col-. Moreover, neither strain grew in cecal luminal contents. Together, these data suggest the possibility that both E. coli F-18 and F-18col- must grow in mucus to colonize the streptomycin-treated mouse large intestine, that E. coli F-18col- is eliminated by E. coli F-18 because it does not grow in mucus as well as E. coli F-18, and that E. coli F-18col- can resist elimination by E. coli F-18 if it is allowed enough time to establish itself within the mucus layer. PMID:3281898

  7. Deep short-read sequencing of chromosome 17 from the mouse strains A/J and CAST/Ei identifies significant germline variation and candidate genes that regulate liver triglyceride levels.

    PubMed

    Sudbery, Ian; Stalker, Jim; Simpson, Jared T; Keane, Thomas; Rust, Alistair G; Hurles, Matthew E; Walter, Klaudia; Lynch, Dee; Teboul, Lydia; Brown, Steve D; Li, Heng; Ning, Zemin; Nadeau, Joseph H; Croniger, Colleen M; Durbin, Richard; Adams, David J

    2009-01-01

    Genome sequences are essential tools for comparative and mutational analyses. Here we present the short read sequence of mouse chromosome 17 from the Mus musculus domesticus derived strain A/J, and the Mus musculus castaneus derived strain CAST/Ei. We describe approaches for the accurate identification of nucleotide and structural variation in the genomes of vertebrate experimental organisms, and show how these techniques can be applied to help prioritize candidate genes within quantitative trait loci. PMID:19825173

  8. Mouse Cyp4a isoforms: enzymatic properties, gender- and strain-specific expression, and role in renal 20-hydroxyeicosatetraenoic acid formation.

    PubMed

    Muller, Dominik N; Schmidt, Cosima; Barbosa-Sicard, Eduardo; Wellner, Maren; Gross, Volkmar; Hercule, Hantz; Markovic, Marija; Honeck, Horst; Luft, Friedrich C; Schunck, Wolf-Hagen

    2007-04-01

    AA (arachidonic acid) hydroxylation to 20-HETE (20-hydroxyeicosatetraenoic acid) influences renal vascular and tubular function. To identify the CYP (cytochrome P450) isoforms catalysing this reaction in the mouse kidney, we analysed the substrate specificity of Cyp4a10, 4a12a, 4a12b and 4a14 and determined sex- and strain-specific expressions. All recombinant enzymes showed high lauric acid hydroxylase activities. Cyp4a12a and Cyp4a12b efficiently hydroxylated AA to 20-HETE with V(max) values of approx. 10 nmol x nmol(-1) x min(-1) and K(m) values of 20-40 microM. 20-Carboxyeicosatetraenoic acid occurred as a secondary metabolite. AA hydroxylase activities were approx. 25-75-fold lower with Cyp4a10 and not detectable with Cyp4a14. Cyp4a12a and Cyp4a12b also efficiently converted EPA (eicosapentaenoic acid) into 19/20-OH- and 17,18-epoxy-EPA. In male mice, renal microsomal AA hydroxylase activities ranged between approx. 100 (NMRI), 45-55 (FVB/N, 129 Sv/J and Balb/c) and 25 pmol x min(-1) x mg(-1) (C57BL/6). The activities correlated with differences in Cyp4a12a protein and mRNA levels. Treatment with 5alpha-dihydrotestosterone induced both 20-HETE production and Cyp4a12a expression more than 4-fold in male C57BL/6 mice. All female mice showed low AA hydroxylase activities (15-25 pmol x min(-1) x mg(-1)) and very low Cyp4a12a mRNA and protein levels, but high Cyp4a10 and Cyp4a14 expression. Renal Cyp4a12b mRNA expression was almost undetectable in both sexes of all strains. Thus Cyp4a12a is the predominant 20-HETE synthase in the mouse kidney. Cyp4a12a expression determines the sex- and strain-specific differences in 20-HETE generation and may explain sex and strain differences in the susceptibility to hypertension and target organ damage. PMID:17112342

  9. Validation of operant social motivation paradigms using BTBR T+tf/J and C57BL/6J inbred mouse strains

    PubMed Central

    Martin, Loren; Sample, Hannah; Gregg, Michael; Wood, Caleb

    2014-01-01

    Background As purported causal factors are identified for autism spectrum disorder (ASD), new assays are needed to better phenotype animal models designed to explore these factors. With recent evidence suggesting that deficits in social motivation are at the core of ASD behavior, the development of quantitative measures of social motivation is particularly important. The goal of our study was to develop and validate novel assays to quantitatively measure social motivation in mice. Methods In order to test the validity of our paradigms, we compared the BTBR strain, with documented social deficits, to the prosocial C57BL/6J strain. Two novel conditioning paradigms were developed that allowed the test mouse to control access to a social partner. In the social motivation task, the test mice lever pressed for a social reward. The reward contingency was set on a progressive ratio of reinforcement and the number of lever presses achieved in the final trial of a testing session (breakpoint) was used as an index of social motivation. In the valence comparison task, motivation for a food reward was compared to a social reward. We also explored activity, social affiliation, and preference for social novelty through a series of tasks using an ANY-Maze video-tracking system in an open-field arena. Results BTBR mice had significantly lower breakpoints in the social motivation paradigm than C57BL/6J mice. However, the valence comparison task revealed that BTBR mice also made significantly fewer lever presses for a food reward. Conclusions The results of the conditioning paradigms suggest that the BTBR strain has an overall deficit in motivated behavior. Furthermore, the results of the open-field observations may suggest that social differences in the BTBR strain are anxiety induced. PMID:25328850

  10. Real-Time PCR Quantification of Heteroplasmy in a Mouse Model with Mitochondrial DNA of C57BL/6 and NZB/BINJ Strains

    PubMed Central

    Sangalli, Juliano Rodrigues; Rodrigues, Thiago Bittencourt; Smith, Lawrence Charles; Meirelles, Flávio Vieira; Chiaratti, Marcos Roberto

    2015-01-01

    Mouse models are widely employed to study mitochondrial inheritance, which have implications to several human diseases caused by mutations in the mitochondrial genome (mtDNA). These mouse models take advantage of polymorphisms between the mtDNA of the NZB/BINJ and the mtDNA of common inbred laboratory (i.e., C57BL/6) strains to generate mice with two mtDNA haplotypes (heteroplasmy). Based on PCR followed by restriction fragment length polymorphism (PCR-RFLP), these studies determine the level of heteroplasmy across generations and in different cell types aiming to understand the mechanisms underlying mitochondrial inheritance. However, PCR-RFLP is a time-consuming method of low sensitivity and accuracy that dependents on the use of restriction enzyme digestions. A more robust method to measure heteroplasmy has been provided by the use of real-time quantitative PCR (qPCR) based on allelic refractory mutation detection system (ARMS-qPCR). Herein, we report an ARMS-qPCR assay for quantification of heteroplasmy using heteroplasmic mice with mtDNA of NZB/BINJ and C57BL/6 origin. Heteroplasmy and mtDNA copy number were estimated in germline and somatic tissues, providing evidence of the reliability of the approach. Furthermore, it enabled single-step quantification of heteroplasmy, with sensitivity to detect as low as 0.1% of either NZB/BINJ or C57BL/6 mtDNA. These findings are relevant as the ARMS-qPCR assay reported here is fully compatible with similar heteroplasmic mouse models used to study mitochondrial inheritance in mammals. PMID:26274500

  11. Proteomic analysis of HDL from inbred mouse strains implicates APOE associated with HDL in reduced cholesterol efflux capacity via the ABCA1 pathway[S

    PubMed Central

    Pamir, Nathalie; Hutchins, Patrick; Ronsein, Graziella; Vaisar, Tomas; Reardon, Catherine A.; Getz, Godfrey S.; Lusis, Aldons J.; Heinecke, Jay W.

    2016-01-01

    Cholesterol efflux capacity associates strongly and negatively with the incidence and prevalence of human CVD. We investigated the relationships of HDL’s size and protein cargo with its cholesterol efflux capacity using APOB-depleted serum and HDLs isolated from five inbred mouse strains with different susceptibilities to atherosclerosis. Like humans, mouse HDL carried >70 proteins linked to lipid metabolism, the acute-phase response, proteinase inhibition, and the immune system. HDL’s content of specific proteins strongly correlated with its size and cholesterol efflux capacity, suggesting that its protein cargo regulates its function. Cholesterol efflux capacity with macrophages strongly and positively correlated with retinol binding protein 4 (RBP4) and PLTP, but not APOA1. In contrast, ABCA1-specific cholesterol efflux correlated strongly with HDL’s content of APOA1, APOC3, and APOD, but not RBP4 and PLTP. Unexpectedly, APOE had a strong negative correlation with ABCA1-specific cholesterol efflux capacity. Moreover, the ABCA1-specific cholesterol efflux capacity of HDL isolated from APOE-deficient mice was significantly greater than that of HDL from wild-type mice. Our observations demonstrate that the HDL-associated APOE regulates HDL’s ABCA1-specific cholesterol efflux capacity. These findings may be clinically relevant because HDL’s APOE content associates with CVD risk and ABCA1 deficiency promotes unregulated cholesterol accumulation in human macrophages. PMID:26673204

  12. The Non-Obese Diabetic Mouse Strain as a Model to Study CD8+ T Cell Function in Relapsing and Progressive Multiple Sclerosis

    PubMed Central

    Ignatius Arokia Doss, Prenitha Mercy; Roy, Andrée-Pascale; Wang, AiLi; Anderson, Ana Carrizosa; Rangachari, Manu

    2015-01-01

    Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on central nervous system (CNS) myelin. Although CD4+ T cell function in MS pathology has been extensively studied, there is also strong evidence that CD8+ T lymphocytes play a key role. Intriguingly, CD8+ T cells accumulate in great numbers in the CNS in progressive MS, a form of the disease that is refractory to current disease-modifying therapies that target the CD4+ T cell response. Here, we discuss the function of CD8+ T cells in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. In particular, we describe EAE in non-obese diabetic (NOD) background mice, which develop a pattern of disease characterized by multiple attacks and remissions followed by a progressively worsening phase. This is highly reminiscent of the pattern of disease observed in nearly half of MS patients. Particular attention is paid to a newly described transgenic mouse strain (1C6) on the NOD background whose CD4+ and CD8+ T cells are directed against the encephalitogenic peptide MOG[35–55]. Use of this model will give us a more complete picture of the role(s) played by distinct T cell subsets in CNS autoimmunity. PMID:26557120

  13. Calcium, potassium, iron, copper and zinc concentrations in the white and gray matter of the cerebellum and corpus callosum in brain of four genetic mouse strains

    NASA Astrophysics Data System (ADS)

    Sergeant, C.; Vesvres, M. H.; Devès, G.; Guillou, F.

    2005-04-01

    In the central nervous system, metallic cations are involved in oligodendrocyte maturation and myelinogenesis. Moreover, the metallic cations have been associated with pathogenesis, particularly multiple sclerosis and malignant gliomas. The brain is vulnerable to either a deficit or an excess of available trace elements. Relationship between trace metals and myelinogenesis is important in understanding a severe human pathology : the multiple sclerosis, which remains without efficient treatment. One approach to understand this disease has used mutant or transgenic mice presenting myelin deficiency or excess. But to date, the concentration of trace metals and mineral elements in white and gray matter areas in wild type brain is unknown. The aim of this study is to establish the reference concentrations of trace metals (iron, copper and zinc) and minerals (potassium and calcium) in the white and gray matter of the mouse cerebellum and corpus callosum. The brains of four different genetic mouse strains (C57Black6/SJL, C57Black6/D2, SJL and C3H) were analyzed. The freeze-dried samples were prepared to allow PIXE (Proton-induced X-ray emission) and RBS (Rutherford backscattering spectrometry) analyses with the nuclear microprobe in Bordeaux. The results obtained give the first reference values. Furthermore, one species out of the fours testes exhibited differences in calcium, iron and zinc concentrations in the white matter.

  14. Complex interplay between brain function and structure during cerebral amyloidosis in APP transgenic mouse strains revealed by multi-parametric MRI comparison.

    PubMed

    Grandjean, Joanes; Derungs, Rebecca; Kulic, Luka; Welt, Tobias; Henkelman, Mark; Nitsch, Roger M; Rudin, Markus

    2016-07-01

    Alzheimer's disease is a fatal neurodegenerative disorder affecting the aging population. Neuroimaging methods, in particular magnetic resonance imaging (MRI), have helped reveal alterations in the brain structure, metabolism, and function of patients and in groups at risk of developing AD, yet the nature of these alterations is poorly understood. Neuroimaging in mice is attractive for investigating mechanisms underlying functional and structural changes associated with AD pathology. Several preclinical murine models of AD have been generated based on transgenic insertion of human mutated APP genes. Depending on the specific mutations, mouse strains express different aspects of amyloid pathology, e.g. intracellular amyloid-β (Aβ) aggregates, parenchymal plaques, or cerebral amyloid angiopathy. We have applied multi-parametric MRI in three transgenic mouse lines to compare changes in brain function with resting-state fMRI and structure with diffusion tensor imaging and high resolution anatomical imaging. E22ΔAβ developing intracellular Aβ aggregates did not present functional or structural alterations compared to their wild-type littermates. PSAPP mice displaying parenchymal amyloid plaques displayed mild functional changes within the supplementary and barrel field cortices, and increased isocortical volume relative to controls. Extensive reduction in functional connectivity in the sensory-motor cortices and within the default mode network, as well as local volume increase in the midbrain relative to wild-type have been observed in ArcAβ mice bearing intracellular Aβ aggregates as well as parenchymal and vascular amyloid deposits. Patterns of functional and structural changes appear to be strain-specific and not directly related to amyloid deposition. PMID:27033685

  15. Interaction of mouse splenocytes and macrophages with bacterial strains in vitro: the effect of age in the immune response.

    PubMed

    Van Beek, A A; Hoogerland, J A; Belzer, C; De Vos, P; De Vos, W M; Savelkoul, H F J; Leenen, P J M

    2016-01-01

    Probiotics influence the immune system, both at the local and systemic level. Recent findings suggest the relation between microbiota and the immune system alters with age. Our objective was to address direct effects of six bacterial strains on immune cells from young and aged mice: Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, Lactococcus lactis MG1363, Bifidobacterium breve ATCC15700, Bifidobacterium infantis ATCC15697, and Akkermansia muciniphila ATCC BAA-835. We used splenocytes and naïve or interferon-γ-stimulated bone marrow-derived macrophages (BMDM) as responder populations. All tested bacterial strains induced phenotypic and cytokine responses in splenocytes and BMDM. Based on magnitude of the cellular inflammatory response and cytokine profiles, two subgroups of bacteria were identified, i.e. L. plantarum and L. casei versus B. breve, B. infantis, and A. muciniphila. The latter group of bacteria induced high levels of cytokines produced under inflammatory conditions, including tumour necrosis factor (TNF), interleukin (IL)-6 and IL-10. Responses to L. lactis showed features of both subgroups. In addition, we compared responses by splenocytes and BMDM derived from young mice to those of aged mice, and found that splenocytes and BMDM derived from aged mice had an increased IL-10 production and dysregulated IL-6 and TNF production compared to young immune cells. Overall, our study shows differential inflammatory responses to distinct bacterial strains, and profound age-dependent effects. These findings, moreover, support the view that immune environment importantly influences bacterial immune effects. PMID:26689225

  16. Amelioration of Colitis in Mouse Model by Exploring Antioxidative Potentials of an Indigenous Probiotic Strain of Lactobacillus fermentum Lf1

    PubMed Central

    Chauhan, Ritu; Sudhakaran Vasanthakumari, Aparna; Panwar, Harsh; Mallapa, Rashmi H.

    2014-01-01

    Based on the preliminary screening of eight indigenous putative probiotic Lactobacilli, Lactobacillus fermentum Lf1 was selected for assessing its antioxidative efficacy in DSS colitis mouse model based on its ability to enhance the expression of “Nrf2” by 6.43-fold and malondialdehyde (MDA) inhibition by 78.1  ±  0.24% in HT-29 cells under H2O2 stress. The Disease Activity Index and histological scores of Lf1-treated mice were lower than the control group. However, expression of “Nrf2” was not observed in Lf1-treated mice. A significant increase in the expression of antioxidative enzymes such as SOD2 and TrxR-1 was recorded in both of the groups. The expression of SOD2 was significantly downregulated in colitis-induced mice by −100.00-fold relative to control group, and the downregulation was considerably reduced to −37.04-fold in colitis Lf1 treatment group. Almost, a similar trend was recorded in case of “thioredoxin” expression, though “CAT” was refractile to expression. The Lf1-treated group had decreased malondialdehyde level as compared to colitis control (37.92  ±  6.31 versus 91.13  ±  5.76 μM/g). These results point towards Lf1-induced activation of the antioxidant enzyme system in the mouse model and its prospects to be explored as a new strategy for IBD management. PMID:25061603

  17. Variation in Taxonomic Composition of the Fecal Microbiota in an Inbred Mouse Strain across Individuals and Time

    PubMed Central

    Hoy, Yana Emmy; Bik, Elisabeth M.; Lawley, Trevor D.; Holmes, Susan P.; Monack, Denise M.

    2015-01-01

    Genetics, diet, and other environmental exposures are thought to be major factors in the development and composition of the intestinal microbiota of animals. However, the relative contributions of these factors in adult animals, as well as variation with time in a variety of important settings, are still not fully understood. We studied a population of inbred, female mice fed the same diet and housed under the same conditions. We collected fecal samples from 46 individual mice over two weeks, sampling four of these mice for periods as long as 236 days for a total of 190 samples, and determined the phylogenetic composition of their microbial communities after analyzing 1,849,990 high-quality pyrosequencing reads of the 16S rRNA gene V3 region. Even under these controlled conditions, we found significant inter-individual variation in community composition, as well as variation within an individual over time, including increases in alpha diversity during the first 2 months of co-habitation. Some variation was explained by mouse membership in different cage and vendor shipment groups. The differences among individual mice from the same shipment group and cage were still significant. Overall, we found that 23% of the variation in intestinal microbiota composition was explained by changes within the fecal microbiota of a mouse over time, 12% was explained by persistent differences among individual mice, 14% by cage, and 18% by shipment group. Our findings suggest that the microbiota of controlled populations of inbred laboratory animals may not be as uniform as previously thought, that animal rearing and handling may account for some variation, and that as yet unidentified factors may explain additional components of variation in the composition of the microbiota within populations and individuals over time. These findings have implications for the design and interpretation of experiments involving laboratory animals. PMID:26565698

  18. Congenic Strains Confirm the Pleiotropic Effect of Chromosome 4 QTL on Mouse Femoral Geometry and Biomechanical Performance

    PubMed Central

    Kristianto, Jasmin; Litscher, Suzanne J.; Johnson, Michael G.; Patel, Forum; Patel, Mital; Fisher, Jacqueline; Zastrow, Ryley K.; Radcliff, Abigail B.; Blank, Robert D.

    2016-01-01

    A pleiotropic quantitative trait locus (QTL) for bone geometry and mechanical performance in mice was mapped to distal chromosome 4 via an intercross of recombinant congenic mice HcB-8 and HcB-23. To study the QTL in isolation, we have generated C3H.B10-(rs6355453-rs13478087) (C.B.4.3) and C3H.B10-(rs6369860-D4Mit170) (C.B.4.2) congenic strains that harbor ~20 Mb and ~3 Mb, respectively, of chromosome 4 overlapping segments from C57BL/10ScSnA (B10) within the locus on a C3H/DiSnA (C3H) background. Using 3-point bend testing and standard beam equations, we phenotyped these mice for femoral mid-diaphyseal geometry and biomechanical performance. We analyzed the results via 2-way ANOVA, using sex and genotype as factors. In the C.B.4.3 strain, we found that homozygous B10/B10 male mice had smaller cross sectional area (CSA) and reduced total displacement than homozygous C3H/C3H mice. Sex by genotype interaction was also observed for maximum load and stiffness for C3H/C3H and B10/B10 mice, respectively. In C.B.4.2 strain, we found that homozygous B10/B10 mice had lower total displacement, post-yield displacement (PYD), stiffness, yield load and maximum load than mice harboring C3H allele. Sex by genotype interaction was observed in B10/B10 mice for perimeter, outer minor axis (OMA) and CSA. There were no significant differences in tissue level mechanical performance, which suggest that the QTL acts primarily on circumferential bone size. These data confirm the prior QTL mapping data and support other work demonstrating the importance of chromosome 4 QTL on bone modeling and bone responses to mechanical loading. PMID:26849124

  19. Systematic Analysis of Gene Expression Differences between Left and Right Atria in Different Mouse Strains and in Human Atrial Tissue

    PubMed Central

    Fabritz, Larissa; Greber, Boris; Schöler, Hans; Scheld, Hans H.; Hoffmeier, Andreas; Brown, Nigel A.; Kirchhof, Paulus

    2011-01-01

    Background Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria. Methods We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery. Results We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFβ family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c+/− atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c. Conclusions Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining

  20. Distinct MHC class I–dependent NK cell–activating receptors control cytomegalovirus infection in different mouse strains

    PubMed Central

    Pyzik, Michał; Charbonneau, Benoit; Gendron-Pontbriand, Eve-Marie; Babić, Marina; Krmpotić, Astrid; Jonjić, Stipan

    2011-01-01

    Recognition of mouse cytomegalovirus (MCMV)–infected cells by activating NK cell receptors was first described in the context of Ly49H, which confers resistance to C57BL/6 mice. We investigated the ability of other activating Ly49 receptors to recognize MCMV-infected cells in mice from various H-2 backgrounds. We observed that Ly49P1 from NOD/Ltj mice, Ly49L from BALB mice, and Ly49D2 from PWK/Pas mice respond to MCMV-infected cells in the context of H-2Dk and the viral protein m04/gp34. Recognition was also seen in the H-2d and/or H-2f contexts, depending on the Ly49 receptor examined, but never in H-2b. Furthermore, BALB.K (H-2k) mice showed reduced viral loads compared with their H-2d or H-2b congenic partners, a reduction which was dependent on interferon γ secretion by Ly49L+ NK cells early after infection. Adoptive transfer of Ly49L+, but not Ly49L−, NK cells significantly increased resistance against MCMV infection in neonate BALB.K mice. These results suggest that multiple activating Ly49 receptors participate in H-2–dependent recognition of MCMV infection, providing a common mechanism of NK cell–mediated resistance against viral infection. PMID:21518798

  1. Experimental Evolution of Legionella pneumophila in Mouse Macrophages Leads to Strains with Altered Determinants of Environmental Survival

    PubMed Central

    Ensminger, Alexander W.; Yassin, Yosuf; Miron, Alexander; Isberg, Ralph R.

    2012-01-01

    The Gram-negative bacterium, Legionella pneumophila, is a protozoan parasite and accidental intracellular pathogen of humans. We propose a model in which cycling through multiple protozoan hosts in the environment holds L. pneumophila in a state of evolutionary stasis as a broad host-range pathogen. Using an experimental evolution approach, we tested this hypothesis by restricting L. pneumophila to growth within mouse macrophages for hundreds of generations. Whole-genome resequencing and high-throughput genotyping identified several parallel adaptive mutations and population dynamics that led to improved replication within macrophages. Based on these results, we provide a detailed view of the population dynamics of an experimentally evolving bacterial population, punctuated by frequent instances of transient clonal interference and selective sweeps. Non-synonymous point mutations in the flagellar regulator, fleN, resulted in increased uptake and broadly increased replication in both macrophages and amoebae. Mutations in multiple steps of the lysine biosynthesis pathway were also independently isolated, resulting in lysine auxotrophy and reduced replication in amoebae. These results demonstrate that under laboratory conditions, host restriction is sufficient to rapidly modify L. pneumophila fitness and host range. We hypothesize that, in the environment, host cycling prevents L. pneumophila host-specialization by maintaining pathways that are deleterious for growth in macrophages and other hosts. PMID:22693450

  2. Cooperative effect of the VP1 amino acids 98E, 145A and 169F in the productive infection of mouse cell lines by enterovirus 71 (BS strain).

    PubMed

    Victorio, Carla Bianca Luena; Xu, Yishi; Ng, Qimei; Meng, Tao; Chow, Vincent Tk; Chua, Kaw Bing

    2016-01-01

    Enterovirus 71 (EV71) is a neurotrophic virus that causes hand, foot and mouth disease (HFMD) and occasional neurological infection among children. It infects primate cells but not rodent cells, primarily due to the incompatibility between the virus and the expressed form of its receptor, scavenger receptor class B member 2 (SCARB2) protein, on rodent cells (mSCARB2). We previously generated adapted strains (EV71:TLLm and EV71:TLLmv) that were shown to productively infect primate and rodent cell lines and whose genomes exhibited a multitude of non-synonymous mutations compared with the EV71:BS parental virus. In this study, we aimed to identify mutations that are necessary for productive infection of murine cells by EV71:BS. Using reverse genetics and site-directed mutagenesis, we constructed EV71 infectious clones with specific mutations that generated amino acid substitutions in the capsid VP1 and VP2 proteins. We subsequently assessed the infection induced by clone-derived viruses (CDVs) in mouse embryonic fibroblast NIH/3T3 and murine neuroblastoma Neuro-2a cell lines. We found that the CDV:BS-VP1(K98E,E145A,L169F) with three substitutions in the VP1 protein-K98E, E145A and L169F-productively infected both mouse cell lines for at least three passages of the virus in murine cells. Moreover, the virus gained the ability to utilize the mSCARB2 protein to infect murine cell lines. These results demonstrate that the three VP1 residues cooperate to effectively interact with the mSCARB2 protein on murine cells and permit the virus to infect murine cells. Gain-of-function studies similar to the present work provide valuable insight into the mutational trajectory required for EV71 to infect new host cells previously non-susceptible to infection. PMID:27329847

  3. Cooperative effect of the VP1 amino acids 98E, 145A and 169F in the productive infection of mouse cell lines by enterovirus 71 (BS strain)

    PubMed Central

    Victorio, Carla Bianca Luena; Xu, Yishi; Ng, Qimei; Meng, Tao; Chow, Vincent TK; Chua, Kaw Bing

    2016-01-01

    Enterovirus 71 (EV71) is a neurotrophic virus that causes hand, foot and mouth disease (HFMD) and occasional neurological infection among children. It infects primate cells but not rodent cells, primarily due to the incompatibility between the virus and the expressed form of its receptor, scavenger receptor class B member 2 (SCARB2) protein, on rodent cells (mSCARB2). We previously generated adapted strains (EV71:TLLm and EV71:TLLmv) that were shown to productively infect primate and rodent cell lines and whose genomes exhibited a multitude of non-synonymous mutations compared with the EV71:BS parental virus. In this study, we aimed to identify mutations that are necessary for productive infection of murine cells by EV71:BS. Using reverse genetics and site-directed mutagenesis, we constructed EV71 infectious clones with specific mutations that generated amino acid substitutions in the capsid VP1 and VP2 proteins. We subsequently assessed the infection induced by clone-derived viruses (CDVs) in mouse embryonic fibroblast NIH/3T3 and murine neuroblastoma Neuro-2a cell lines. We found that the CDV:BS-VP1K98E,E145A,L169F with three substitutions in the VP1 protein—K98E, E145A and L169F—productively infected both mouse cell lines for at least three passages of the virus in murine cells. Moreover, the virus gained the ability to utilize the mSCARB2 protein to infect murine cell lines. These results demonstrate that the three VP1 residues cooperate to effectively interact with the mSCARB2 protein on murine cells and permit the virus to infect murine cells. Gain-of-function studies similar to the present work provide valuable insight into the mutational trajectory required for EV71 to infect new host cells previously non-susceptible to infection. PMID:27329847

  4. Infection with a Mouse-Adapted Strain of the 2009 Pandemic Virus Causes a Highly Severe Disease Associated with an Impaired T Cell Response

    PubMed Central

    Meunier, Isabelle; Morisseau, Olivier; Garneau, Émilie; Marois, Isabelle; Cloutier, Alexandre; Richter, Martin V.

    2015-01-01

    Despite a relatively low fatality rate, the 2009 H1N1 pandemic virus differed from other seasonal viruses in that it caused mortality and severe pneumonia in the young and middle-aged population (18–59 years old). The mechanisms underlying this increased disease severity are still poorly understood. In this study, a human isolate of the 2009 H1N1 pandemic virus was adapted to the mouse (MAp2009). The pathogenicity of the MAp2009 virus and the host immune responses were evaluated in the mouse model and compared to the laboratory H1N1 strain A/Puerto Rico/8/1934 (PR8). The MAp2009 virus reached consistently higher titers in the lungs over 14 days compared to the PR8 virus, and caused severe disease associated with high morbidity and 85% mortality rate, contrasting with the 0% death rate in the PR8 group. During the early phase of infection, both viruses induced similar pathology in the lungs. However, MAp2009-induced lung inflammation was sustained until the end of the study (day 14), while there was no sign of inflammation in the PR8-infected group by day 10. Furthermore, at day 3 post-infection, MAp2009 induced up to 10- to 40-fold more cytokine and chemokine gene expression, respectively. More importantly, the numbers of CD4+ T cells and virus-specific CD8+ T cells were significantly lower in the lungs of MAp2009-infected mice compared to PR8-infected mice. Interestingly, there was no difference in the number of dendritic cells in the lung and in the draining lymph node. Moreover, mice infected with PR8 or MAp2009 had similar numbers of CCR5 and CXCR3-expressing T cells, suggesting that the impaired T cell response was not due to a lack of chemokine responsiveness or priming of T cells. This study demonstrates that a mouse-adapted virus from an isolate of the 2009 pandemic virus interferes with the adaptive immune response leading to a more severe disease. PMID:26381265

  5. Parvovirus minute virus of mice strain i multiplication and pathogenesis in the newborn mouse brain are restricted to proliferative areas and to migratory cerebellar young neurons.

    PubMed Central

    Ramírez, J C; Fairén, A; Almendral, J M

    1996-01-01

    Newborn BALB/c mice intranasally inoculated at birth with a lethal dose of the immunosuppressive strain of the parvovirus minute virus of mice (MVMi) developed motor disabilities and intention tremors with a high incidence by the day 6 postinfection (dpi). These neurological syndromes paralleled the synthesis of virus intermediate DNA replicative forms and yield of infectious particles in the brain, with kinetics that peaked by this time. The preferred virus replicative sites in the brain were established early in the infection (2 dpi) and at the onset of clinical symptoms (6 dpi) and were compared with major regions of cellular proliferative activity found after intraperitoneal injection of bromodeoxyuridine 24 h before encephalons were subjected to immunohistochemistry detection. At 2 dpi, viral capsid antigen was located in the laterodorsal thalamic and the pontine nuclei but not in the extensive proliferative regions of the mouse brain at this postnatal day. At 6 dpi, however, the neurotropism of the MVMi was highlighted by its ability to target the subventricular zone of the ventricles, the subependymal zone of the olfactory bulb, and the dentate gyrus of the hippocampus, which are the three main germinal centers of the cerebrum in mouse postbirth neurogenesis. Unexpectedly, in the cerebellum, the MVMi capsid antigen was confined exclusively to cells that have undergone mitosis and have migrated to the internal granular layer (IGL) and not to the proliferative external granular layer (EGL), which was stained with antiproliferative cell nuclear antigen antibody and is the main target in other parvovirus infections. This result implies temporal or differentiation coupling between MVMi cycle and neuroblast morphogenesis, since proliferative granules of the EGL should primarily be infected but must migrate in a virus carrier state into the IGL in order to express the capsid proteins. During migration, many cells undergo destruction, accounting for the marked

  6. Intestinal Microbial Dysbiosis and Colonic Epithelial Cell Hyperproliferation by Dietary α-Mangostin is Independent of Mouse Strain

    PubMed Central

    Gutierrez-Orozco, Fabiola; Thomas-Ahner, Jennifer M.; Galley, Jeffrey D.; Bailey, Michael T.; Clinton, Steven K.; Lesinski, Gregory B.; Failla, Mark L.

    2015-01-01

    Beverages and supplements prepared from mangosteen fruit are claimed to support gut health and immunity, despite the absence of supporting evidence from clinical trials. We recently reported that α-mangostin (α-MG), the most abundant xanthone in mangosteen fruit, altered the intestinal microbiome, promoted dysbiosis, and exacerbated colitis in C57BL/6J mice. The objective of this study was to determine whether induction of dysbiosis by dietary α-MG is limited to the C57BL/6J strain or represents a more generic response to chronic intake of the xanthone on the gut microbiota of mice. C3H, Balb/c, Nude FoxN1nu, and C57BL/6J mice, each demonstrating unique microbiomes, were fed standard diet or diet containing 0.1% α-MG for four weeks. Dietary α-MG significantly altered the cecal and colonic microbiota in all four strains of mice, promoting a reduction in generally assumed beneficial bacterial groups while increasing the abundance of pathogenic bacteria. Consumption of α-MG was associated with reduced abundance of Firmicutes and increased abundance of Proteobacteria. The abundance of Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae was reduced in α-MG-fed mice, while that of Enterobacteriaceae and Enterococcaceae was increased. Dietary α-MG also was associated with increased proliferation of colonic epithelial cells, infiltration of immune cells, infiltration of immune cells and increased fluid content in stool. These results suggest that ingestion of pharmacologic doses of xanthones in mangosteen-containing supplements may adversely alter the gut microbiota and should be used with caution. PMID:25621505

  7. Intestinal microbial dysbiosis and colonic epithelial cell hyperproliferation by dietary α-mangostin is independent of mouse strain.

    PubMed

    Gutierrez-Orozco, Fabiola; Thomas-Ahner, Jennifer M; Galley, Jeffrey D; Bailey, Michael T; Clinton, Steven K; Lesinski, Gregory B; Failla, Mark L

    2015-01-01

    Beverages and supplements prepared from mangosteen fruit are claimed to support gut health and immunity, despite the absence of supporting evidence from clinical trials. We recently reported that α-mangostin (α-MG), the most abundant xanthone in mangosteen fruit, altered the intestinal microbiome, promoted dysbiosis, and exacerbated colitis in C57BL/6J mice. The objective of this study was to determine whether induction of dysbiosis by dietary α-MG is limited to the C57BL/6J strain or represents a more generic response to chronic intake of the xanthone on the gut microbiota of mice. C3H, Balb/c, Nude FoxN1nu, and C57BL/6J mice, each demonstrating unique microbiomes, were fed standard diet or diet containing 0.1% α-MG for four weeks. Dietary α-MG significantly altered the cecal and colonic microbiota in all four strains of mice, promoting a reduction in generally assumed beneficial bacterial groups while increasing the abundance of pathogenic bacteria. Consumption of α-MG was associated with reduced abundance of Firmicutes and increased abundance of Proteobacteria. The abundance of Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae was reduced in α-MG-fed mice, while that of Enterobacteriaceae and Enterococcaceae was increased. Dietary α-MG also was associated with increased proliferation of colonic epithelial cells, infiltration of immune cells, infiltration of immune cells and increased fluid content in stool. These results suggest that ingestion of pharmacologic doses of xanthones in mangosteen-containing supplements may adversely alter the gut microbiota and should be used with caution. PMID:25621505

  8. Effect of vitamin K2 on the development of stress-induced osteopenia in a growing senescence-accelerated mouse prone 6 strain

    PubMed Central

    KATSUYAMA, HIRONOBU; FUSHIMI, SHIGEKO; YAMANE, KUNIKAZU; WATANABE, YOKO; SHIMOYA, KOICHIRO; OKUYAMA, TOSHIKO; KATSUYAMA, MIDORI; SAIJOH, KIYOFUMI; TOMITA, MASAFUMI

    2015-01-01

    Vitamin K2 (VK2) has been used as a therapeutic agent for osteoporosis, since it has been suggested to be able to reduce the frequency of fractures by improving bone quality; however, bone turnover is strictly regulated by various cytokines and hormones. In the present study, the effect of menaquinone-4 (MK-4) on bone turnover was investigated using the senescence-accelerated mouse prone 6 (SAMP6) strain. Since water-immersion restraint stress (WRS) causes a significant decrease in bone mineral density (BMD), WRS was used as the bone resorption model in the SAMP6 strain. Six-week-old SAMP6 male mice were divided into the following three groups: Control, WRS and WRS + MK-4. WRS was performed for 6 h per day, 5 times a week, for 4 weeks. Following WRS, MK-4 (30 mg/kg) was injected subcutaneously 3 times a week for 4 weeks. No growth retardation was observed in the WRS groups as compared with the control group. In the WRS groups, the BMD was significantly lower than that in the control group. The levels of bone formation and resorption markers were increased in the WRS groups, indicating that WRS reduced the BMD by promoting high bone turnover. A bone histomorphometrical examination showed that the trabecular (Tb) bone mass in the secondary spongiosa at the distal femur was significantly reduced in the WRS mice, and this reduction was abrogated by MK-4 treatment. Specifically, the Tb bone reduction was caused by the activation of osteoclasts (Ocs), and Oc activity was suppressed by MK-4. The number of osteoblasts and the mineral apposition rate were significantly increased in the WRS and WRS + MK-4 mice, suggesting that WRS triggered a significantly higher mineral apposition rate. These results indicate that MK-4 can induce recovery from the bone mineral loss caused by WRS treatment. Further studies are required to clarify the association between bone quality and MK-4. PMID:26622403

  9. Reporter mouse strain provides a novel look at angiotensin type-2 receptor distribution in the central nervous system.

    PubMed

    de Kloet, Annette D; Wang, Lei; Ludin, Jacob A; Smith, Justin A; Pioquinto, David J; Hiller, Helmut; Steckelings, U Muscha; Scheuer, Deborah A; Sumners, Colin; Krause, Eric G

    2016-03-01

    Angiotensin-II acts at its type-1 receptor (AT1R) in the brain to regulate body fluid homeostasis, sympathetic outflow and blood pressure. However, the role of the angiotensin type-2 receptor (AT2R) in the neural control of these processes has received far less attention, largely because of limited ability to effectively localize these receptors at a cellular level in the brain. The present studies combine the use of a bacterial artificial chromosome transgenic AT2R-enhanced green fluorescent protein (eGFP) reporter mouse with recent advances in in situ hybridization (ISH) to circumvent this obstacle. Dual immunohistochemistry (IHC)/ISH studies conducted in AT2R-eGFP reporter mice found that eGFP and AT2R mRNA were highly co-localized within the brain. Qualitative analysis of eGFP immunoreactivity in the brain then revealed localization to neurons within nuclei that regulate blood pressure, metabolism, and fluid balance (e.g., NTS and median preoptic nucleus [MnPO]), as well as limbic and cortical areas known to impact stress responding and mood. Subsequently, dual IHC/ISH studies uncovered the phenotype of specific populations of AT2R-eGFP cells. For example, within the NTS, AT2R-eGFP neurons primarily express glutamic acid decarboxylase-1 (80.3 ± 2.8 %), while a smaller subset express vesicular glutamate transporter-2 (18.2 ± 2.9 %) or AT1R (8.7 ± 1.0 %). No co-localization was observed with tyrosine hydroxylase in the NTS. Although AT2R-eGFP neurons were not observed within the paraventricular nucleus (PVN) of the hypothalamus, eGFP immunoreactivity is localized to efferents terminating in the PVN and within GABAergic neurons surrounding this nucleus. These studies demonstrate that central AT2R are positioned to regulate blood pressure, metabolism, and stress responses. PMID:25427952

  10. Mouse Hepatitis Virus Strain A59 and Blocking Antireceptor Monoclonal Antibody Bind to the N-Terminal Domain of Cellular Receptor

    NASA Astrophysics Data System (ADS)

    Dveksler, Gabriela S.; Pensiero, Michael N.; Dieffenbach, Carl W.; Cardellichio, Christine B.; Basile, Alexis A.; Elia, Patrick E.; Holmes, Kathryn V.

    1993-03-01

    Mouse hepatitis virus (MHV) strain A59 uses as cellular receptors members of the carcinoembryonic antigen family in the immunoglobulin superfamily. Recombinant receptor proteins with deletions of whole or partial immunoglobulin domains were used to identify the regions of receptor glycoprotein recognized by virus and by antireceptor monoclonal antibody CC1, which blocks infection of murine cells. Monoclonal antibody CC1 and MHV-A59 virions bound only to recombinant proteins containing the entire first domain of MHV receptor. To determine which of the proteins could serve as functional virus receptors, receptor-negative hamster cells were transfected with recombinant deletion clones and then challenged with MHV-A59 virions. Receptor activity required the entire N-terminal domain with either the second or the fourth domain and the transmembrane and cytoplasmic domains. Recombinant proteins lacking the first domain or its C-terminal portion did not serve as viral receptors. Thus, like other virus receptors in the immunoglobulin superfamily, including CD4, poliovirus receptor, and intercellular adhesion molecule 1, the N-terminal domain of MHV receptor is recognized by the virus and the blocking monoclonal antibody.

  11. Novel frame-shift mutation in Slc5a2 encoding SGLT2 in a strain of senescence-accelerated mouse SAMP10.

    PubMed

    Unno, Keiko; Yamamoto, Hiroyuki; Toda, Masateru; Hagiwara, Shiori; Iguchi, Kazuaki; Hoshino, Minoru; Takabayashi, Fumiyo; Hasegawa-Ishii, Sanae; Shimada, Atsuyoshi; Hosokawa, Masanori; Higuchi, Keiichi; Mori, Masayuki

    2014-11-01

    The senescence-accelerated mouse prone10 (SAMP10) strain, a model of aging, exhibits cognitive impairments and cerebral atrophy. We noticed that SAMP10/TaSlc mice, a SAMP10 substrain, have developed persistent glucosuria over the past few years. In the present study, we characterized SAMP10/TaSlc mice and further identified a spontaneous mutation in the Slc5a2 gene encoding sodium-glucose co-transporter (SGLT) 2. The mean concentration of urine glucose was high in SAMP10/TaSlc mice and increased further with advancing age, whereas other strains of senescence-accelerated mice, including SAMP1/SkuSlc, SAMP6/TaSlc and SAMP8/TaSlc or normal aging control SAMR1/TaSlc mice, exhibited no detectable glucose in urine. SAMP10/TaSlc mice consumed increasing amounts of food and water compared to SAMR1/TaSlc mice, suggesting the compensation of polyuria and the loss of glucose. Oral glucose tolerance tests showed decreased glucose reabsorption in the kidney of SAMP10/TaSlc mice. In addition, blood glucose levels decreased in an age-dependent fashion. The kidney was innately larger than that of control mice with no histological alterations. We examined the expression levels of glucose transporters in the kidney. Among SGLT1, SGLT2, glucose transporter (GLUT) 1 and GLUT2, we found a significant decrease only in the level of SGLT2. DNA sequencing of SGLT2 in SAMP10/TaSlc mice revealed a single nucleotide deletion of guanine at 1236, which resulted in a frameshift mutation that produced a truncated protein. We designate this strain as SAMP10/TaSlc-Slc5a2(slc) (SAMP10-ΔSglt2). Recently, SGLT2 inhibitors have been demonstrated to be effective for the treatment of patients with type 2 diabetes (T2D). SAMP10-ΔSglt2 mice may serve as a unique preclinical model to study the link between aging-related neurodegenerative disorders and T2D. PMID:25450362

  12. Mouse Strain Impacts Fatty Acid Uptake and Trafficking in Liver, Heart, and Brain: A Comparison of C57BL/6 and Swiss Webster Mice.

    PubMed

    Seeger, D R; Murphy, E J

    2016-05-01

    C57BL/6 and Swiss Webster mice are used to study lipid metabolism, although differences in fatty acid uptake between these strains have not been reported. Using a steady state kinetic model, [1-(14)C]16:0, [1-(14)C]20:4n-6, or [1-(14)C]22:6n-3 was infused into awake, adult male mice and uptake into liver, heart, and brain determined. The integrated area of [1-(14)C]20:4n-6 in plasma was significantly increased in C57BL/6 mice, but [1-(14)C]16:0 and [1-(14)C]22:6n-3 were not different between groups. In heart, uptake of [1-(14)C]20:4n-6 was increased 1.7-fold in C57BL/6 mice. However, trafficking of [1-(14)C]22:6n-3 into the organic fraction of heart was significantly decreased 33 % in C57BL/6 mice. Although there were limited differences in fatty acid tracer trafficking in liver or brain, [1-(14)C]16:0 incorporation into liver neutral lipids was decreased 18 % in C57BL/6 mice. In heart, the amount of [1-(14)C]16:0 and [1-(14)C]22:6n-3 incorporated into total phospholipids were decreased 45 and 49 %, respectively, in C57BL/6 mice. This was accounted for by a 53 and 37 % decrease in [1-(14)C]16:0 and 44 and 52 % decrease in [1-(14)C]22:6n-3 entering ethanolamine glycerophospholipids and choline glycerophospholipids, respectively. In contrast, there was a significant increase in [1-(14)C]20:4n-6 esterification into all heart phospholipids of C57BL/6 mice. Although changes in uptake were limited to heart, several significant differences were found in fatty acid trafficking into heart, liver, and brain phospholipids. In summary, our data demonstrates differences in tissue fatty acid uptake and trafficking between mouse strains is an important consideration when carrying out fatty acid metabolic studies. PMID:26797754

  13. Emotion and Cognition in High and Low Stress Sensitive Mouse Strains: A Combined Neuroendocrine and Behavioral Study in BALB/c and C57BL/6J Mice

    PubMed Central

    Brinks, Vera; van der Mark, Maaike; de Kloet, Ronald; Oitzl, Melly

    2007-01-01

    Emotionally arousing experiences and stress influence cognitive processes and vice versa. Understanding the relations and interactions between these three systems forms the core of this study. We tested two inbred mouse strains (BALB/c, C57BL/6J; male; 3-month-old) for glucocorticoid stress system markers (expression of MR and GR mRNA and protein in hippocampus, amygdala, and prefrontal cortex; blood plasma corticosterone), used behavioral tasks for emotions and cognitive performance (elevated plus maze, holeboard) to assess the interdependence of these factors. We hypothesize that BALB/c mice have a stress-vulnerable neuroendocrine phenotype and that emotional expressions in BALB/c and C57BL/6J mice will differentially contribute to learning and memory. We applied factor analyses on emotional and cognitive parameters to determine the behavioral structure of BALB/c and C57BL/6J mice. Glucocorticoid stress system markers indeed show that BALB/c mice are more stress-vulnerable than C57BL/6J mice. Moreover, emotional and explorative factors differed between naïve BALB/c and C57BL/6J mice. BALB/c mice display high movement in anxiogenic zones and high risk assessment, while C57BL/6J mice show little movement in anxiogenic zones and display high vertical exploration. Furthermore, BALB/c mice are superior learners, showing learning related behavior which is highly structured and emotionally biased when exposed to a novel or changing situation. In contrast, C57BL/6J mice display a rather “chaotic” behavioral structure during learning in absence of an emotional factor. These results show that stress vulnerability coincides with more emotionality, which drives well orchestrated goal directed behavior to the benefit of cognition. Both phenotypes have their advantage depending on environmental demands. PMID:18958190

  14. Isolation and Characterization of a Novel Strain of Mesenchymal Stem Cells from Mouse Umbilical Cord: Potential Application in Cell-Based Therapy

    PubMed Central

    Li, Wen-Wen; Wei, Yau-Huei; Li, Hung; Lai, Dar-Ming; Lin, Teng-Nan

    2013-01-01

    Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have recently been recognized as a potential source for cell-based therapy in various preclinical animal models, such as Parkinson’s disease, cerebral ischemia, spinal cord injury, and liver failure; however, the precise cellular and molecular mechanisms underlying the beneficial outcomes remain under investigation. There is a growing concern regarding rejection and alteration of genetic code using this xenotransplantation approach. In this study, a novel strain of murine MSCs derived from the umbilical cord of wild-type and green fluorescent protein (GFP) transgenic mice have been successfully isolated, expanded, and characterized. After 10 passages, the mUC-MSCs developed a rather homogeneous, triangular, spindle-shaped morphology, and were sub-cultured up to 7 months (over 50 passages) without overt changes in morphology and doubling time. Cell surface markers are quite similar to MSCs isolated from other tissue origins as well as hUC-MSCs. These mUC-MSCs can differentiate into osteoblasts, adipocytes, neurons, and astrocytes in vitro, as well as hematopoietic lineage cells in vivo. mUC-MSCs also possess therapeutic potential against two disease models, focal ischemic stroke induced by middle cerebral artery occlusion (MCAo) and acute hepatic failure. Subtle differences in the expression of cytokine-related genes exist between mUC-MSCs and hUC-MSCs, which may retard and jeopardize the advance of cell therapy. Allografts of these newly established mUC-MSCs into various mouse disease models may deepen our insights into the development of more effective cell therapy regimens. PMID:23991222

  15. Effect of GDNF on depressive-like behavior, spatial learning and key genes of the brain dopamine system in genetically predisposed to behavioral disorders mouse strains.

    PubMed

    Naumenko, Vladimir S; Kondaurova, Elena M; Bazovkina, Daria V; Tsybko, Anton S; Ilchibaeva, Tatyana V; Khotskin, Nikita V; Semenova, Alina A; Popova, Nina K

    2014-11-01

    The effect of glial cell line-derived neurotrophic factor (GDNF) on behavior and brain dopamine system in predisposed to depressive-like behavior ASC (Antidepressant Sensitive Cataleptics) mice in comparison with the parental "nondepressive" CBA mice was studied. In 7days after administration (800ng, i.c.v.) GDNF decreased escape latency time and the path traveled to reach hidden platform in Morris water maze in ASC mice. GDNF enhanced depressive-like behavioral traits in both "nondepressive" CBA and "depressive" ASC mice. In CBA mice, GDNF decreased functional response to agonists of D1 (chloro-APB hydrobromide) and D2 (sumanirole maleate) receptors in tail suspension test, reduced D2 receptor gene expression in the substantia nigra and increased monoamine oxydase A (MAO A) gene expression in the striatum. GDNF increased D1 and D2 receptor genes expression in the nucleus accumbens of ASC mice but failed to alter expression of catechol-O-methyltransferase, dopamine transporter, MAO B and tyrosine hydroxylase genes in both investigated mouse strains. Thus, GDNF produced long-term genotype-dependent effect on behavior and the brain dopamine system. GDNF pretreatment (1) reduced D1 and D2 receptors functional responses and D2 receptor gene expression in s. nigra of CBA mice; (2) increased D1 and D2 receptor genes expression in n. accumbens of ASC mice and (3) improved spatial learning in ASC mice. GDNF enhanced depressive-like behavior both in CBA and ASC mice. The data suggest that genetically defined variance in the cross-talk between GDNF and brain dopamine system contributes to the variability of GDNF-induced responses and might be responsible for controversial GDNF effects. PMID:25101543

  16. Association of H2A{sup b} with resistance to collagen-induced arthritis in H2-recombinant mouse strains: An allele associated with reduction of several apparently unrelated responses

    SciTech Connect

    Mitchison, N.A.; Brunner, M.C.

    1995-02-01

    HLA class II alleles can protect against immunological diseases. Seeking an animal model for a naturally occurring protective allele, we screened a panel of H2-congenic and recombinant mouse strains for ability to protect against collagen-induced arthritis. The strains were crossed with the susceptible strain DBA/1, and the F{sub 1} hybrids immunized with cattle and chicken type II collagen. Hybrids having the H2A{sup b} allele displayed a reduced incidence and duration of the disease. They also had a reduced level of pre-disease inflammation, but not of anti-collagen antibodies. The allele is already known to be associated with reduction of other apparently unrelated immune responses, suggesting that some form of functional differentiation may operate that is not exclusively related to epitope-binding. It is suggested that this may reflect allelic variation in the class II major histocompatibility complex promoter region. 42 refs., 7 figs., 1 tab.

  17. CYCLOPENTA[CD]PYRENE-INDUCED TUMORIGENICITY, KI-RAS CODON 12 MUTATIONS AND DNA ADDUCTS IN STRAIN A/J MOUSE LUNG

    EPA Science Inventory

    Cyclopenta[cd]pyrene (CPP) is a ubiquitous cyclopenta-fused polycyclic aromatic hydrocarbon. PP is highly genotoxic in bacterial and mammalian systems inducing gene mutations, sister-chromatid exchanges, and morphological transformation. PP is a mouse skin carcinogen, a mouse ski...

  18. In vivo colonization of the mouse large intestine and in vitro penetration of intestinal mucus by an avirulent smooth strain of Salmonella typhimurium and its lipopolysaccharide-deficient mutant.

    PubMed Central

    Nevola, J J; Laux, D C; Cohen, P S

    1987-01-01

    The relative abilities of an avirulent Salmonella typhimurium strain with wild-type lipopolysaccharide (LPS) character, SL5319, and a nearly isogenic LPS-deficient mutant, SL5325, to colonize the large intestines of streptomycin-treated CD-1 mice in vivo and to penetrate colonic mucus in vitro were studied. Previously it had been shown that, when fed simultaneously to streptomycin-treated mice (approximately 10(10) CFU each), the S. typhimurium strain with wild-type LPS colonized at 10(8) CFU/g of feces indefinitely, whereas the LPS-deficient mutant dropped within 3 days to a level of only 10(4) CFU/g of feces. In the present investigation, when SL5325 was allowed to colonize for 8 days before feeding mice SL5319 or when it was fed to mice simultaneously with an Escherichia coli strain of human fecal origin (10(10) CFU each), both strains colonized indefinitely at 10(7) CFU/g of feces. Moreover, when the wild-type and LPS-deficient mutant strains were fed to mice simultaneously in low numbers (approximately 10(5) CFU each) the strains survived equally well in the large intestines for 8 days, after which the LPS-deficient mutant was eliminated (less than 10(2) CFU/g of feces), whereas the wild-type colonized at a level of 10(7) CFU/g of feces. In addition although both strains were able to adhere to mucus and epithelial cell preparations in vitro, the wild-type strain was shown to have greater motility and chemotactic activity on CD-1 mouse colonic mucus in vitro and to more rapidly penetrate and form a stable association with immobilized colonic mucosal components in vitro. Based on these data, we suggest that the ability of an S. typhimurium strain to colonize the streptomycin-treated mouse large intestine may, in part, depend on its ability to penetrate deeply into the mucus layer on the intestinal wall and subsequently, through growth, colonize the mucosa. PMID:3316026

  19. Intra- and extracellular activities of dicloxacillin and linezolid against a clinical Staphylococcus aureus strain with a small-colony-variant phenotype in an in vitro model of THP-1 macrophages and an in vivo mouse peritonitis model.

    PubMed

    Sandberg, Anne; Lemaire, Sandrine; Van Bambeke, Françoise; Tulkens, Paul M; Hughes, Diarmaid; von Eiff, Christof; Frimodt-Møller, Niels

    2011-04-01

    The small-colony-variant (SCV) phenotype of Staphylococcus aureus has been associated with difficult-to-treat infections, reduced antimicrobial susceptibility, and intracellular persistence. This study represents a detailed intra- and extracellular investigation of a clinical wild-type (WT) S. aureus strain and its counterpart with an SCV phenotype both in vitro and in vivo, using the THP-1 cell line model and the mouse peritonitis model, respectively. Bacteria of both phenotypes infected the mouse peritoneum intra- and extracellularly. The SCV phenotype was less virulent and showed distinct bacterial clearance, a reduced multiplication capacity, and a reduced internalization ability. However, some of the SCV-infected mice were still culture positive up to 96 h postinfection, and bacteria of this phenotype could spread to the mouse kidney and furthermore revert to the more virulent WT phenotype in both the mouse peritoneum and kidney. The SCV phenotype is therefore, despite reduced virulence, an important player in S. aureus pathogenesis. In the THP-1 cell line model, both dicloxacillin (DCX) and linezolid (LZD) reduced the intracellular inocula of bacteria of both phenotypes by approximately 1 to 1.5 log(10) in vitro, while DCX was considerably more effective against extracellular bacteria. In the mouse peritonitis model, DCX and LZD were also able to control both intra- and extracellular infections caused by either phenotype. Treatment with a single dose of DCX and LZD was, however, insufficient to clear the SCVs in the kidneys, and the risk of recurrent infection remained. This stresses the importance of an optimal dosing of the antibiotic when SCVs are present. PMID:21282430

  20. Disruption of overlapping transcripts in the ROSA βgeo 26 gene trap strain leads to widespread expression of β-galactosidase in mouse embryos and hematopoietic cells

    PubMed Central

    Zambrowicz, Brian P.; Imamoto, Akira; Fiering, Steve; Herzenberg, Leonard A.; Kerr, William G.; Soriano, Philippe

    1997-01-01

    The ROSAβgeo26 (ROSA26) mouse strain was produced by random retroviral gene trapping in embryonic stem cells. Staining of ROSA26 tissues and fluorescence-activated cell sorter-Gal analysis of hematopoietic cells demonstrates ubiquitous expression of the proviral βgeo reporter gene, and bone marrow transfer experiments illustrate the general utility of this strain for chimera and transplantation studies. The gene trap vector has integrated into a region that produces three transcripts. Two transcripts, lost in ROSA26 homozygous animals, originate from a common promoter and share identical 5′ ends, but neither contains a significant ORF. The third transcript, originating from the reverse strand, shares antisense sequences with one of the noncoding transcripts. This third transcript potentially encodes a novel protein of at least 505 amino acids that is conserved in humans and in Caenorhabditis elegans. PMID:9108056

  1. Mouse strain differences in immobility and sensitivity to fluvoxamine and desipramine in the forced swimming test: analysis of serotonin and noradrenaline transporter binding.

    PubMed

    Sugimoto, Yumi; Kajiwara, Yoshinobu; Hirano, Kazufumi; Yamada, Shizuo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hotta, Yoshihiro; Yamada, Jun

    2008-09-11

    Strain differences in immobility time in the forced swimming test were investigated in five strains of mice, namely, ICR, ddY, C57BL/6, DBA/2 and BALB/c mice. There were significant strain differences. The immobility times of ICR, ddY and C57BL/6 mice were longer than those of DBA/2 and BALB/c mice. Immobility times were not significantly related to locomotor activity in these strains. There were also differences in sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine. In ICR, ddY and C57BL/6 mice, fluvoxamine did not affect immobility time, while it reduced the immobility time of DBA/2 and BALB/c mice dose-dependently. The noradrenaline reuptake inhibitor desipramine decreased immobility time in all strains of mice. Serotonin (5-HT) transporter binding in the brains of all five strains of mice was also investigated. Analysis of 5-HT transporter binding revealed significant strain differences, being lower in DBA/2 and BALB/c mice than in other strains of mice. The amount of 5-HT transporter binding was correlated to baseline immobility time. However, there was no significant relation between noradrenaline transporter binding and immobility time. These results suggest that the duration of baseline immobility depends on the levels of 5-HT transporter binding, leading to apparent strain differences in immobility time in the forced swimming test. Furthermore, differences in 5-HT transporter binding may cause variations in responses to fluvoxamine. PMID:18655786

  2. Comparison of BALB/c and B6-albino mouse strain blastocysts as hosts for the injection of C57BL6/N-derived C2 embryonic stem cells.

    PubMed

    Alcantar, Tuija M; Wiler, Rhonda; Rairdan, Xin Y

    2016-08-01

    Embryonic stem (ES) cells from a C57BL/6N (B6N) background injected into B6(Cg)-Tyrc-2J/J (B6-albino) recipient blastocysts are commonly used for generating genetically modified mouse models. To understand the influence of the recipient blastocyst strain on germline transmission, BALB/cAnNTac and B6-albino germline transmission rates were compared using the C57BL6/N-derived C2 ES cell line. A total of 92 ES cell clones from 27 constructs were injected. We compared blastocyst yield, birth rate, chimera formation rate, and high-percentage (>50 %) male chimera formation rate. For germline transmission, we analyzed 24 clones from 19 constructs, which generated high-percentage male chimeras from both donor strains. B6-albino hosts resulted in higher mean blastocyst yields per donor than did BALB/c ones (3.6 vs. 2.5). However, BALB/c hosts resulted in a higher birth rate than B6-albino ones (36 vs. 27 %), a higher chimera formation rate (50 vs. 42 %), a higher high-percentage male chimera rate (10 vs. 8 %), and a higher germline transmission rate (65 vs. 49 %), respectively. Our data suggest that BALB/c is a suitable blastocyst host strain for C2 ES cells and has an advantage over the B6-albino strain for receiving the injection of C2 ES cells. PMID:26852382

  3. Lipopolysaccharide structures of Helicobacter pylori genomic strains 26695 and J99, mouse model H. pylori Sydney strain, H. pylori P466 carrying sialyl Lewis X, and H. pylori UA915 expressing Lewis B classification of H. pylori lipopolysaccharides into glycotype families.

    PubMed

    Monteiro, M A; Appelmelk, B J; Rasko, D A; Moran, A P; Hynes, S O; MacLean, L L; Chan, K H; Michael, F S; Logan, S M; O'Rourke, J; Lee, A; Taylor, D E; Perry, M B

    2000-01-01

    This study describes the molecular makeup of the cell-wall lipopolysaccharides (LPSs) (O-chain polysaccharide-->core oligosaccharide-->lipid A) from five Helicobacter pylori strains: H. pylori 26695 and J99, the complete genome sequences of which have been published, the established mouse model Sydney strain (SS1), and the symptomatic strains P466 and UA915. All chemical and serological experiments were performed on the intact LPSs. H. pylori 26695 and SS1 possessed either a low-Mr semi-rough-form LPS carrying mostly a single Ley type-2 blood-group determinant in the O-chain region covalently attached to the core oligosaccharide or a high-Mr smooth-form LPS, as did strain J99, with an elongated partially fucosylated type-2 N-acetyllactosamine (polyLacNAc) O-chain polymer, terminated mainly by a Lex blood-group determinant, connected to the core oligosaccharide. In the midst of semi-rough-form LPS glycoforms, H. pylori 26695 and SS1 also expressed in the O-chain region a difucosylated antigen, alpha-L-Fucp(1-3)-alpha-L-Fucp(1-4)-beta-D-GlcpNAc, and the cancer-cell-related type-1 or type-2 linear B-blood-group antigen, alpha-D-Galp(1-3)-beta-D-Galp(1-3 or 4)-beta-D-GlcpNAc. The LPS of H. pylori strain P466 carried the cancer-associated type-2 sialyl Lex blood-group antigen, and the LPS from strain UA915 expressed a type-1 Leb blood-group unit. These findings should aid investigations that focus on identifying and characterizing genes responsible for LPS biosynthesis in genomic strains 26695 and J99, and in understanding the role of H. pylori LPS in animal model studies. The LPSs from the H. pylori strains studied to date were grouped into specific glycotype families. PMID:10632700

  4. Harvard U.'s Request for Commercial Rights to New Strain of Mouse Forces Debate in Europe over Whether Animals Can Be Patented.

    ERIC Educational Resources Information Center

    Chronicle of Higher Education, 1989

    1989-01-01

    The European Patent Convention has informed Harvard University that its application for a patent on a genetically engineered mouse may be refused. The application was the first to obtain patent protection across most of Europe for a transgenic animal, one which has been implanted with genes from another animal. (MSE)

  5. Development of a live, attenuated, potential vaccine strain of R. equi expressing vapA and the virR operon, and virulence assessment in the mouse.

    PubMed

    Whitehead, Ashley E; Parreira, Valeria R; Hewson, Joanne; Watson, Johanna L; Prescott, John F

    2012-01-15

    Pneumonia caused by Rhodococcus equi remains a significant problem in foals. The objective of this study was to develop a safe and efficacious attenuated strain of R. equi for eventual use in oral immunization of foals. The approach involved expression of vapA in a live, virulence plasmid-negative, strain of R. equi (strain 103-). PCR-amplified fragments of the vapA gene, with and without the upstream genes virR, orf5, vapH, orf7 and orf8 (orf4-8), were cloned into a shuttle vector pNBV1. These plasmids, named pAW48A and pAWVapA respectively, were electroporated into strain 103-. The presence of the recombinant vectors in the attenuated strain (103-) and the integrity of the inserted genes were confirmed, and both constructs expressed VapA. The virulence of the two strains was compared to that of wild type R. equi 103+ and negative controls by their intravenous inoculation into mice, followed by examination of liver clearance 4 days later. Mice inoculated with R. equi 103-, 103-/pAWVapA and 103-/pNBV1 completely cleared infection, whereas strain 103-/pAW48A persisted in 47% of mice. PMID:22088674

  6. Growth-inhibitory activity of the D-mannan of Saccharomyces cerevisiae X2180-1A-5 mutant strain against mouse-implanted sarcoma 180 and Ehrlich-carcinoma solid tumor.

    PubMed

    Matsumoto, T; Takanohashi, M; Okubo, Y; Suzuki, M; Suzuki, S

    1980-08-15

    The D-mannan of Saccharomyces cerevisiae X2180-1A-5 mutant strain, which possesses a main chain composed of alpha-(1 yields 6) linked D-mannopyranosyl residues and a small proportion of branches composed of alpha-(1 yields 2)- and alpha-(1 yields 3)-linked D-mannopyranosyl residues, showed strong growth-inhibitory activity against mouse-implanted Sarcoma 180 and Ehrlich-carcinoma solid tumor. The observation that the level of this activity was nearly identical with that of the D-mannan of a wild-type strain of bakers' yeast, which possesses a high proportion of branches composed of alpha-(1 yields 2)-and alpha-(1 yields 3)-linked D-mannopyranosyl residues, suggests that the branches are not essential for antitumor activity. The partial acid-degradation products of both D-mannans, the molecular weight of which was one-third of that of each parent D-mannan, had only one half of the antitumor activity of the parent D-mannans. This suggests that molecular size is the most important factor for the differences in acitvity of the polysaccharides of wild and mutant strains. PMID:6996813

  7. QTL Analysis of Type I and Type IIA Fibers in Soleus Muscle in a Cross between LG/J and SM/J Mouse Strains

    PubMed Central

    Carroll, Andrew M.; Palmer, Abraham A.; Lionikas, Arimantas

    2011-01-01

    Properties of muscle fibers, i.e., their type, number and size, are important determinants of functional characteristics of skeletal muscle, and of the quality of meat in livestock. Genetic factors play an important role in determining variation in fiber properties, however, specific genes remain largely elusive. We examined histological properties of soleus muscle fibers in two strains of mice exhibiting a twofold difference in muscle mass, LG/J and SM/J, and their F2 intercross. The total number of muscle fibers (555 ± 106; mean ± SD) did not differ between the strains or between males and females. A higher percentage of type I fibers was observed in the LG/J compared to the SM/J strain (P < 0.001) in both males (45 ± 3 vs. 37 ± 4%) and females (58 ± 4 vs. 41 ± 3%). Across strains, females had a higher percentage of type I fibers than males (P < 0.001), and the sex effect was greater in the LG/J strain (strain-by-sex interaction, P < 0.001). The cross-sectional area (CSA) did not differ between type I and type IIA fibers, but was greater in the LG/J than the SM/J strain (1365 ± 268 vs. 825 ± 229 μm2, P < 0.001). Three significant quantitative trait locus (QTL) affecting CSA for type I and type IIA fibers mapped to chromosomes (Chr) 1, 6, and 11 and three suggestive QTL for percentage of type I fibers mapped to Chr 2, 3, and 4. Within each significant QTL, regions of conserved synteny were also implicated in variation of similar traits in an analogous study in pigs. Our results provide the evidence that the intercross between the SM/J and LG/J strains is a promising model to search for genes affecting muscle fiber properties. PMID:22303393

  8. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain.

    PubMed

    Pichery, Mélanie; Mirey, Emilie; Mercier, Pascale; Lefrancais, Emma; Dujardin, Arnaud; Ortega, Nathalie; Girard, Jean-Philippe

    2012-04-01

    IL-33 (previously known as NF from high endothelial venules) is an IL-1 family cytokine that signals through the ST2 receptor and drives cytokine production in mast cells, basophils, eosinophils, invariant NKT and NK cells, Th2 lymphocytes, and type 2 innate immune cells (natural helper cells, nuocytes, and innate helper 2 cells). Little is known about endogenous IL-33; for instance, the cellular sources of IL-33 in mouse tissues have not yet been defined. In this study, we generated an Il-33-LacZ gene trap reporter strain (Il-33(Gt/Gt)) and used this novel tool to analyze expression of endogenous IL-33 in vivo. We found that the Il-33 promoter exhibits constitutive activity in mouse lymphoid organs, epithelial barrier tissues, brain, and embryos. Immunostaining with anti-IL-33 Abs, using Il-33(Gt/Gt) (Il-33-deficient) mice as control, revealed that endogenous IL-33 protein is highly expressed in mouse epithelial barrier tissues, including stratified squamous epithelia from vagina and skin, as well as cuboidal epithelium from lung, stomach, and salivary gland. Constitutive expression of IL-33 was not detected in blood vessels, revealing the existence of species-specific differences between humans and mice. Importantly, IL-33 protein was always localized in the nucleus of producing cells with no evidence for cytoplasmic localization. Finally, strong expression of the Il-33-LacZ reporter was also observed in inflamed tissues, in the liver during LPS-induced endotoxin shock, and in the lung alveoli during papain-induced allergic airway inflammation. Together, our findings support the possibility that IL-33 may function as a nuclear alarmin to alert the innate immune system after injury or infection in epithelial barrier tissues. PMID:22371395

  9. Coculture of Escherichia coli O157:H7 with a Nonpathogenic E. coli Strain Increases Toxin Production and Virulence in a Germfree Mouse Model

    PubMed Central

    Goswami, Kakolie; Chen, Chun; Xiaoli, Lingzi; Eaton, Kathryn A.

    2015-01-01

    Escherichia coli O157:H7 is a notorious foodborne pathogen due to its low infectious dose and the disease symptoms it causes, which include bloody diarrhea and severe abdominal cramps. In some cases, the disease progresses to hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS), due to the expression of one or more Shiga toxins (Stx). Isoforms of Stx, including Stx2a, are encoded within temperate prophages. In the presence of certain antibiotics, phage induction occurs, which also increases the expression of toxin genes. Additionally, increased Stx2 accumulation has been reported when O157:H7 was cocultured with phage-susceptible nonpathogenic E. coli. This study characterized an E. coli O157:H7 strain, designated PA2, that belongs to the hypervirulent clade 8 cluster. Stx2a levels after ciprofloxacin induction were lower for PA2 than for the prototypical outbreak strains Sakai and EDL933. However, during coculture with the nonpathogenic strain E. coli C600, PA2 produced Stx2a levels that were 2- to 12-fold higher than those observed during coculture with EDL933 and Sakai, respectively. Germfree mice cocolonized by PA2 and C600 showed greater kidney damage, increased Stx2a accumulation in feces, and more visible signs of disease than mice given PA2 or C600 alone. These data suggest one mechanism by which microorganisms associated with the colonic microbiota could enhance the virulence of E. coli O157:H7, particularly a subset of clade 8 strains. PMID:26259815

  10. The ROP18 and ROP5 allele types are highly predictive of mouse-virulence across globally distributed strains of Toxoplasma gondii

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The protozoan parasite Toxoplasma gondii is one of the known most successful eukaryotic pathogens on Earth. Virulence of T. gondii strains varies greatly in mice, and mounting evidence suggests that such variations may be relevant to the manifestation of human toxoplasmosis. Polymorphic rhoptry-secr...

  11. Coculture of Escherichia coli O157:H7 with a Nonpathogenic E. coli Strain Increases Toxin Production and Virulence in a Germfree Mouse Model.

    PubMed

    Goswami, Kakolie; Chen, Chun; Xiaoli, Lingzi; Eaton, Kathryn A; Dudley, Edward G

    2015-11-01

    Escherichia coli O157:H7 is a notorious foodborne pathogen due to its low infectious dose and the disease symptoms it causes, which include bloody diarrhea and severe abdominal cramps. In some cases, the disease progresses to hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS), due to the expression of one or more Shiga toxins (Stx). Isoforms of Stx, including Stx2a, are encoded within temperate prophages. In the presence of certain antibiotics, phage induction occurs, which also increases the expression of toxin genes. Additionally, increased Stx2 accumulation has been reported when O157:H7 was cocultured with phage-susceptible nonpathogenic E. coli. This study characterized an E. coli O157:H7 strain, designated PA2, that belongs to the hypervirulent clade 8 cluster. Stx2a levels after ciprofloxacin induction were lower for PA2 than for the prototypical outbreak strains Sakai and EDL933. However, during coculture with the nonpathogenic strain E. coli C600, PA2 produced Stx2a levels that were 2- to 12-fold higher than those observed during coculture with EDL933 and Sakai, respectively. Germfree mice cocolonized by PA2 and C600 showed greater kidney damage, increased Stx2a accumulation in feces, and more visible signs of disease than mice given PA2 or C600 alone. These data suggest one mechanism by which microorganisms associated with the colonic microbiota could enhance the virulence of E. coli O157:H7, particularly a subset of clade 8 strains. PMID:26259815

  12. Dextran Sodium Sulfate-Induced Inflammation Alters the Expression of Proteins by Intestinal Escherichia coli Strains in a Gnotobiotic Mouse Model

    PubMed Central

    Schumann, Sara; Alpert, Carl; Engst, Wolfram; Loh, Gunnar

    2012-01-01

    To identify Escherichia coli proteins involved in adaptation to intestinal inflammation, mice were monoassociated with the colitogenic E. coli strain UNC or with the probiotic E. coli strain Nissle. Intestinal inflammation was induced by treating the mice with 3.5% dextran sodium sulfate (DSS). Differentially expressed proteins in E. coli strains collected from cecal contents were identified by 2-dimensional difference gel electrophoresis. In both strains, acute inflammation led to the downregulation of pathways involved in carbohydrate breakdown and energy generation. Accordingly, DSS-treated mice had lower concentrations of bacterial fermentation products in their cecal contents than control mice. Differentially expressed proteins also included the Fe-S cluster repair protein NfuA, the tryptophanase TnaA, and the uncharacterized protein YggE. NfuA expression was 3-fold higher in E. coli strains from DSS-treated than from control mice. Reporter experiments confirmed the induction of nfuA in response to iron deprivation, mimicking Fe-S cluster destruction by inflammation. YggE expression, which has been reported to reduce the intracellular level of reactive oxygen species, was 4- to 8-fold higher in E. coli Nissle than in E. coli UNC. This was confirmed by in vitro reporter gene assays indicating that Nissle is better equipped to cope with oxidative stress than UNC. Nissle isolated from DSS-treated and control mice had TnaA levels 4- to 7-fold-higher than those of UNC. Levels of indole resulting from the TnaA reaction were higher in control animals associated with E. coli Nissle. Because of its anti-inflammatory effect, indole is hypothesized to be involved in the extension of the remission phase in ulcerative colitis described for E. coli Nissle. PMID:22210207

  13. The in vitro and in vivo effects of constitutive light expression on a bioluminescent strain of the mouse enteropathogen Citrobacter rodentium.

    PubMed

    Read, Hannah M; Mills, Grant; Johnson, Sarah; Tsai, Peter; Dalton, James; Barquist, Lars; Print, Cristin G; Patrick, Wayne M; Wiles, Siouxsie

    2016-01-01

    Bioluminescent reporter genes, such as those from fireflies and bacteria, let researchers use light production as a non-invasive and non-destructive surrogate measure of microbial numbers in a wide variety of environments. As bioluminescence needs microbial metabolites, tagging microorganisms with luciferases means only live metabolically active cells are detected. Despite the wide use of bioluminescent reporter genes, very little is known about the impact of continuous (also called constitutive) light expression on tagged bacteria. We have previously made a bioluminescent strain of Citrobacter rodentium, a bacterium which infects laboratory mice in a similar way to how enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) infect humans. In this study, we compared the growth of the bioluminescent C. rodentium strain ICC180 with its non-bioluminescent parent (strain ICC169) in a wide variety of environments. To understand more about the metabolic burden of expressing light, we also compared the growth profiles of the two strains under approximately 2,000 different conditions. We found that constitutive light expression in ICC180 was near-neutral in almost every non-toxic environment tested. However, we also found that the non-bioluminescent parent strain has a competitive advantage over ICC180 during infection of adult mice, although this was not enough for ICC180 to be completely outcompeted. In conclusion, our data suggest that constitutive light expression is not metabolically costly to C. rodentium and supports the view that bioluminescent versions of microbes can be used as a substitute for their non-bioluminescent parents to study bacterial behaviour in a wide variety of environments. PMID:27366640

  14. The in vitro and in vivo effects of constitutive light expression on a bioluminescent strain of the mouse enteropathogen Citrobacter rodentium

    PubMed Central

    Read, Hannah M.; Mills, Grant; Johnson, Sarah; Tsai, Peter; Dalton, James; Barquist, Lars; Print, Cristin G.; Patrick, Wayne M.

    2016-01-01

    Bioluminescent reporter genes, such as those from fireflies and bacteria, let researchers use light production as a non-invasive and non-destructive surrogate measure of microbial numbers in a wide variety of environments. As bioluminescence needs microbial metabolites, tagging microorganisms with luciferases means only live metabolically active cells are detected. Despite the wide use of bioluminescent reporter genes, very little is known about the impact of continuous (also called constitutive) light expression on tagged bacteria. We have previously made a bioluminescent strain of Citrobacter rodentium, a bacterium which infects laboratory mice in a similar way to how enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) infect humans. In this study, we compared the growth of the bioluminescent C. rodentium strain ICC180 with its non-bioluminescent parent (strain ICC169) in a wide variety of environments. To understand more about the metabolic burden of expressing light, we also compared the growth profiles of the two strains under approximately 2,000 different conditions. We found that constitutive light expression in ICC180 was near-neutral in almost every non-toxic environment tested. However, we also found that the non-bioluminescent parent strain has a competitive advantage over ICC180 during infection of adult mice, although this was not enough for ICC180 to be completely outcompeted. In conclusion, our data suggest that constitutive light expression is not metabolically costly to C. rodentium and supports the view that bioluminescent versions of microbes can be used as a substitute for their non-bioluminescent parents to study bacterial behaviour in a wide variety of environments. PMID:27366640

  15. Two new behavioral QTLs, Emo4 and Reb1, map to mouse Chromosome 1: Congenic strains and candidate gene identification studies.

    PubMed

    de Ledesma, Ana Maria Rodriguez; Desai, Aarti N; Bolivar, Valerie J; Symula, Derek J; Flaherty, Lorraine

    2006-02-01

    By use of newly developed subcongenic strains of mice from a parental B6.129-Il10-/- knockout/congenic strain, we have narrowed the critical region for a new behavioral QTL, called Emo4, for open-field activity to a segment of Chromosome 1 between Erbb4 (68.4Mb) and B3gnt7 (86.2 Mb). We have also uncovered an additional QTL governing repetitive beam breaks in the open field. This QTL, called Reb1, maps to the interval between Asb1 (91.4 Mb) and NM_172851 (100.0 Mb) and is one of the first QTLs mapped for this type of behavior. Genome-wide microarray expression analyses were then undertaken to help to identify candidate genes that may be the cause of these genetic differences in open-field performance. In this effort, we analyzed global gene expression differences in the amygdalae by use of Affymetrix GeneChips between B6, B6.129-Il10-/-, and B6.129R4. Several probe sets representing target Chr 1 genes were found that showed significantly differential expression in the subcongenic and congenic strains. Several candidate genes have been identified. One of these regions coincides with an homologous region in humans that has been associated with autism, a disease whose symptoms include repetitive actions. This study illustrates that the use of congenic strains combined with global gene expression analyses can produce a list of viable candidates. It further shows that caution should be observed when analyzing the effects of knockout/congenic strains because many of the gene expression differences in these comparisons could not be attributable to the ablated Il10 gene but rather to passenger gene effects. PMID:16465591

  16. Increased expression of the Vesicular Glutamate Transporter-1 (VGLUT1) in the prefrontal cortex correlates with differential vulnerability to chronic stress in various mouse strains: effects of fluoxetine and MK-801.

    PubMed

    Farley, Séverine; Dumas, Sylvie; El Mestikawy, Salah; Giros, Bruno

    2012-01-01

    supports the conclusion that BDNF and VGLUT1 are depressive state markers, but not involved in its etiology. Finally, there is a substantial similarity between the phenotypes that are observed in the BALB/c mice and endogenous depression in humans, as well as between C57BL/6 mice and atypical depression. To have a better understanding of the variability of depression etiologies in human, and the implication of the glutamatergic system, it may be suggested that future animal studies in the mouse would systematically compare the two strains BALB/c and C57BL/6 for the identification of relevant biological mechanisms. This article is part of a special Issue entitled 'Anxiety and Depression'. PMID:21945287

  17. A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease.

    PubMed

    Calvert, Amanda E; Dixon, Kandice L; Piper, Joseph; Bennett, Susan L; Thibodeaux, Brett A; Barrett, Alan D T; Roehrig, John T; Blair, Carol D

    2016-07-01

    The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection. To counteract possible selection of 17D-204 variants that escape neutralization by treatment with a single MAb (2C9-cIgG), we developed a second cMAb, 864-cIgG, for use in combination with 2C9-cIgG in post-vaccinal therapy. MAb 864-cIgG recognizes/neutralizes only YFV 17D-204 vaccine substrain and binds to domain III (DIII) of the viral envelope protein, which is different from the YFV type-specific binding site of 2C9-cIgG in DII. Although it neutralized 17D-204 in vitro, administration of 864-cIgG had no protective capacity in the interferon receptor-deficient AG129 mouse model of 17D-204 infection. The data presented here show that although DIII-specific 864-cIgG neutralizes virus infectivity in vitro, it does not have the ability to abrogate disease in vivo. Therefore, combination of 864-cIgG with 2C9-cIgG for treatment of YF vaccination SAEs does not appear to provide an improvement on 2C9-cIgG therapy alone. PMID:27126613

  18. Virulence of 32 Salmonella Strains in Mice

    PubMed Central

    Swearingen, Matthew C.; Porwollik, Steffen; Desai, Prerak T.; McClelland, Michael; Ahmer, Brian M. M.

    2012-01-01

    Virulence and persistence in the BALB/c mouse gut was tested for 32 strains of Salmonella enterica for which genome sequencing is complete or underway, including 17 serovars within subspecies I (enterica), and two representatives of each of the other five subspecies. Only serovar Paratyphi C strain BAA1715 and serovar Typhimurium strain 14028 were fully virulent in mice. Three divergent atypical Enteritidis strains were not virulent in BALB/c, but two efficiently persisted. Most of the other strains in all six subspecies persisted in the mouse intestinal tract for several weeks in multiple repeat experiments although the frequency and level of persistence varied considerably. Strains with heavily degraded genomes persisted very poorly, if at all. None of the strains tested provided immunity to Typhimurium infection. These data greatly expand on the known significant strain-to-strain variation in mouse virulence and highlight the need for comparative genomic and phenotypic studies. PMID:22558320

  19. The relationship between adjunctive drinking, blood ethanol concentration and plasma corticosterone across fixed-time intervals of food delivery in two inbred mouse strains

    PubMed Central

    Ford, Matthew M.; Steele, Andrea M.; McCracken, Aubrey D.; Finn, Deborah A.; Grant, Kathleen A.

    2013-01-01

    Summary Schedules of intermittent food delivery induce excessive fluid intake, termed schedule-induced polydipsia (SIP), and hypothalamic-pituitary-adrenal (HPA) axis activation is important for the expression and maintenance of this adjunctive behavior. Previous work has focused of examining the relationship between water intake and plasma corticosterone (CORT) in rats at a single or a limited range of fixed time (FT) intervals. However, little remains known regarding SIP and the corresponding stress response 1) across the bitonic function that epitomizes adjunctive behavior, 2) when ethanol is the available fluid, and 3) when a species other than rat or multiple strains are studied. Here we report the findings from ethanol-preferring C57BL/6J (B6) and non-preferring DBA/2J (D2) mice serially exposed to progressively larger FT intervals (0 → 60 min) and given access to either water or a 5% v/v ethanol solution. Following 2 weeks of experience with each schedule, blood samples were collected at the conclusion of the last 60-min session to evaluate CORT and the blood ethanol concentration (BEC) achieved. While both strains exhibited a bitonic function of ethanol intake and BEC that peaked at or near a 5-min interval, only D2 mice showed a similar response with water. In contrast, CORT levels rose monotonically with incremental increases in the FT interval regardless of the strain examined or fluid type offered, indicating that glucocorticoid release likely reflects the aversive aspects of increasing intervals between reinforcement rather than engagement in adjunctive behavior. These findings also caution against the use of a single intensity stressor to evaluate the relationship between stress and ethanol intake, as the magnitude of stress appears to affect ethanol consumption in a non-linear fashion. PMID:23827168

  20. Analysis of Individual Mouse Activity in Group Housed Animals of Different Inbred Strains using a Novel Automated Home Cage Analysis System

    PubMed Central

    Bains, Rasneer S.; Cater, Heather L.; Sillito, Rowland R.; Chartsias, Agisilaos; Sneddon, Duncan; Concas, Danilo; Keskivali-Bond, Piia; Lukins, Timothy C.; Wells, Sara; Acevedo Arozena, Abraham; Nolan, Patrick M.; Armstrong, J. Douglas

    2016-01-01

    Central nervous system disorders such as autism as well as the range of neurodegenerative diseases such as Huntington's disease are commonly investigated using genetically altered mouse models. The current system for characterizing these mice usually involves removing the animals from their home-cage environment and placing them into novel environments where they undergo a battery of tests measuring a range of behavioral and physical phenotypes. These tests are often only conducted for short periods of times in social isolation. However, human manifestations of such disorders are often characterized by multiple phenotypes, presented over long periods of time and leading to significant social impacts. Here, we have developed a system which will allow the automated monitoring of individual mice housed socially in the cage they are reared and housed in, within established social groups and over long periods of time. We demonstrate that the system accurately reports individual locomotor behavior within the group and that the measurements taken can provide unique insights into the effects of genetic background on individual and group behavior not previously recognized. PMID:27375446

  1. Analysis of the Fam181 gene family during mouse development reveals distinct strain-specific expression patterns, suggesting a role in nervous system development and function.

    PubMed

    Marks, Matthias; Pennimpede, Tracie; Lange, Lisette; Grote, Phillip; Herrmann, Bernhard G; Wittler, Lars

    2016-01-10

    During somitogenesis differential gene expression can be observed for so-called cyclic genes, which display expression changes with a periodicity of 120min in the mouse. In screens to identify novel cyclic genes in murine embryos, Fam181b was predicted to be an oscillating gene in the presomitic mesoderm (psm). This gene, and its closely related paralog Fam181a, belong to the thus far uncharacterized Fam181 gene family. Here we describe the expression of Fam181b and Fam181a during murine embryonic development. In addition, we confirm oscillation of Fam181b in the psm in-phase with targets of, and regulated by, Notch signaling. Fam181b expression in the psm, as well as in the lateral plate mesoderm, was found to be affected by genetic background. We show that Fam181a and b exhibit partially overlapping mRNA expression patterns, and encode for proteins containing highly-conserved motifs, which predominantly localize to the nucleus. A Fam181b loss-of-function model was generated and found to result in no obvious phenotype. PMID:26407640

  2. The mouse genome informatics and the mouse genome database

    SciTech Connect

    Maltais, L.J.; Blackburn, R.E.; Bradt, D.W.

    1994-09-01

    The Mouse Genome Database (MGD) is a centralized, comprehensive database of the mouse genome that includes genetic mapping data, comparative mapping data, gene descriptions, mutant phenotype descriptions, strains and allelic polymorphism data, inbred strain characteristics, physical mapping data, and molecular probes and clones data. Data in MGD are obtained from the published literature and by electronic transfer from laboratories working on large backcross panels of mice. MGD provides tools that enable the user to search the database, retrieve data, generate reports, analyze data, annotate records, and build genetic maps. The Encyclopedia of the Mouse Genome provides a graphic user interface to mouse genome data. It consists of software tools including: LinkMap, a graphic display of genetic linkage maps with the ability to magnify regions of high locus density: CytoMap, a graphic display of cytogenetic maps showing banded chromosomes with cytogenetic locations of genes and chromosomal aberrations; CATS, a catalog searching tool for text retrieval of mouse locus descriptions. These software tools provide access to the following data sets: Chromosome Committee Reports, MIT Genome Center data, GBASE reports, Mouse Locus Catalog (MLC), and Mouse Cytogenetic Mapping Data. The MGD is available to the scientific community through the World Wide Web (WWW) and Gopher. In addition GBASE can be accessed via the Internet.

  3. Opportunistic bacterial infections in breeding colonies of the NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mouse strain

    PubMed Central

    foreman, Oded; Kavirayani, Anoop M; Griffey, Stephen M; Reader, Rachel; Shultz, Leonard D

    2011-01-01

    Spontaneous morbidity primarily affecting female breeders in three independent breeding colonies of NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice prompted an investigation to uncover the cause of disease. Necropsies were performed on 264 (157 female and 107 male) spontaneously sick, experimentally unmanipulated NSG mice. 42 (15.9%) of the mice had acute or chronic renal inflammatory lesions. 12 of the mice with nephritis had concurrent histologic evidence of an ascending urinary tract infection. From 94 kidneys cultured for bacterial organisms, 23 (24.4%) grew Enterococcus species and 19 (20%) grew Klebsiella Oxytoca. Female mice were twice more likely to present with nephritis than males. These findings indicate that bacterial nephritis is a major contributor to morbidity in the NSG strain. PMID:20817888

  4. Echinococcus multilocularis: parasite-specific humoral and cellular immune response subsets in mouse strains susceptible (AKR, C57B1/6J) or 'resistant' (C57B1/10) to secondary alveolar echinococcosis.

    PubMed Central

    Gottstein, B; Wunderlin, E; Tanner, I

    1994-01-01

    Parasite-specific humoral and cell-mediated immune responses were investigated in highly susceptible (AKR and C57B1/6J) and relatively resistant (C57B1/10) mice undergoing secondary alveolar echinococcosis (infection with Echinococcus multilocularis metacestode). The parasite-specific proliferative immune response of lymph node cells upon in vitro antigen stimulation remained weak in all three mouse strains. By day 30 p.i., CD4+ lymphoblast cells dominated the total population of blast cells in all three mouse strains. There was, however, an unexpectedly high proportion of CD8+ blast cells; by day 90 p.i., a marked proportional increase in CD8+ cells was seen in susceptible (AKR and C57B1/6J), but not in resistant (C57B1/10) mice. Susceptible, but not resistant mice exhibited a significantly decreased responsiveness of lymph node cells to concanavalin A (Con A) stimulation on day 90 p.i. Analysis of the humoral immune response by ELISA showed that resistance in C57B1/10 mice was associated with the ability of the host to synthesize antibodies to Em2 of the IgG3 and IgG1 isotype. Em2 is a lectin-binding carbohydrate antigen of the laminated layer. In susceptible AKR and C57B1/6J mice, low levels of anti-Em2 antibodies of the IgG2a isotype were detected. Anti-Em2 antibodies of the IgG3/IgG1 isotype, however, were absent. Differences in subclass-specific IgG responses were confirmed by immunoblot analyses. Our findings suggest that differences in antigen recognition (with respect to subsets of humoral and cellular immune components), probably controlled by non-H-2 gene(s), coupled to immune suppression modulated by CD8+ cells and/or respective cytokines, may determine susceptibility or resistance in experimental infection with E. multilocularis. Images Fig. 3 Fig. 5 PMID:7910534

  5. CD8+-T-Cell-Dependent Control of Trypanosoma cruzi Infection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2

    PubMed Central

    Araújo, Adriano F. S.; de Alencar, Bruna C. G.; Vasconcelos, José Ronnie C.; Hiyane, Meire I.; Marinho, Cláudio R. F.; Penido, Marcus L. O.; Boscardin, Silvia B.; Hoft, Daniel F.; Gazzinelli, Ricardo T.; Rodrigues, Mauricio M.

    2005-01-01

    We previously described that DNA vaccination with the gene encoding amastigote surface protein 2 (ASP-2) protects approximately 65% of highly susceptible A/Sn mice against the lethal Trypanosoma cruzi infection. Here, we explored the possibility that bacterial recombinant proteins of ASP-2 could be used to improve the efficacy of vaccinations. Initially, we compared the protective efficacy of vaccination regimens using either a plasmid DNA, a recombinant protein, or both sequentially (DNA priming and protein boosting). Survival after the challenge was not statistically different among the three mouse groups and ranged from 53.5 to 75%. The fact that immunization with a recombinant protein alone induced protective immunity revealed the possibility that this strategy could be pursued for vaccination. We investigated this possibility by using six different recombinant proteins representing distinct portions of ASP-2. The vaccination of mice with glutathione S-transferase fusion proteins representing amino acids 261 to 500 or 261 to 380 of ASP-2 in the presence of the adjuvants alum and CpG oligodeoxynucleotide 1826 provided remarkable immunity, consistently protecting 100% of the A/Sn mice. Immunity was completely reversed by the in vivo depletion of CD8+ T cells, but not CD4+ T cells, and was associated with the presence of CD8+ T cells specific for an epitope located between amino acids 320 and 327 of ASP-2. We concluded that a relatively simple formulation consisting of a recombinant protein with a selected portion of ASP-2, alum, and CpG oligodeoxynucleotide 1826 might be used to cross-prime strong CD8+-T-cell-dependent protective immunity against T. cruzi infection. PMID:16113322

  6. Phase III Clinical Trials Comparing the Immunogenicity and Safety of the Vero Cell-Derived Japanese Encephalitis Vaccine Encevac with Those of Mouse Brain-Derived Vaccine by Using the Beijing-1 Strain

    PubMed Central

    Miyazaki, Chiaki; Okada, Kenji; Ozaki, Takao; Hirose, Mizuo; Iribe, Kaneshige; Ishikawa, Yuji; Togashi, Takehiro; Ueda, Kohji

    2014-01-01

    The immunogenicity and safety of an inactivated cell culture Japanese encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical multicenter trials conducted in children. The vaccines contain the same Japanese encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children. Each subject was injected with 17 μg per dose of either CC-JEV or MB-JEV, and the immunogenicity and safety of the vaccines were investigated. Trial 1 showed that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose. Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine that has had a good track record regarding its efficacy for a long time, trial 2 was conducted in 484 healthy children. To improve the stability, CC-JEV was converted from a liquid type to a freeze-dried type of vaccine. Each subject was injected subcutaneously with either 4 μg per dose of CC-JEV, 8 μg per dose of CC-JEV, or 17 μg per dose of MB-JEV twice, at an interval of 2 to 4 weeks, followed by an additional booster immunization 1 to 15 months after the primary immunization. Based on the results of trial 2, 4 μg per dose of the freeze-dried CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV. Encevac was approved and launched in 2011 and has since been in use as a 2nd-generation Japanese encephalitis vaccine in Japan. (These studies have been registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI-080586 for trials 1 and 2, respectively.) PMID:24334689

  7. Prenatal diethylstilbestrol induces malformation of the external genitalia of male and female mice and persistent second-generation developmental abnormalities of the external genitalia in two mouse strains

    PubMed Central

    Mahawong, Phitsanu; Sinclair, Adriane; Li, Yi; Schlomer, Bruce; Rodriguez, Esequiel; Max, Ferretti M.; Liu, Baomei; Baskin, Laurence S.; Cunha, Gerald R.

    2014-01-01

    Potential trans-generational influence of diethylstilbestrol (DES) exposure emerged with reports of effects in grandchildren of DES-treated pregnant women and of reproductive tract tumors in offspring of mice exposed in utero to DES. Accordingly, we examined the trans-generational influence of DES on development of external genitalia (ExG) and compared effects of in utero DES exposure in CD-1 and C57BL/6 mice injected with oil or DES every other day from gestational days 12 to 18. Mice were examined at birth, and on 5 to 120 days postnatal to evaluate ExG malformations. Of 23 adult (≥60 days) prenatally DES-exposed males, features indicative of urethral meatal hypospadias (see text for definitions) ranged from 18 to 100% in prenatally DES-exposed CD-1 males and 31 to 100% in prenatally DES-exposed C57BL/6 males. Thus, the strains differed in the incidence of male urethral hypospadias. Ninety-one percent of DES-exposed CD-1 females and 100% of DES-exposed C57BL/6 females had urethral-vaginal fistula. All DES-exposed CD-1 and C57BL/6 females lacked an os clitoris. None of the prenatally oil-treated CD-1 and C57BL/6 male and female mice had ExG malformations. For the second-generation study, 10 adult CD-1 males and females, from oil- and DES-exposed groups, respectively, were paired with untreated CD-1 mice for 30 days, and their offspring evaluated for ExG malformations. None of the F1 DES-treated females were fertile. Nine of 10 prenatally DES-exposed CD-1 males sired offspring with untreated females, producing 55 male and 42 female pups. Of the F2 DES-lineage adult males, 20% had exposed urethral flaps, a criterion of urethral meatal hypospadias. Five of 42 (11.9%) F2 DES lineage females had urethral-vaginal fistula. In contrast, all F2 oil-lineage males and all oil-lineage females were normal. Thus, prenatal DES exposure induces malformations of ExG in both sexes and strains of mice, and certain malformations are transmitted to the second-generation. PMID

  8. Polygenic inheritance of sensorineural hearing loss (Snhl2, -3, and -4) and organ of Corti patterning defect in the ALR/LtJ mouse strain.

    PubMed

    Latoche, Joseph R; Neely, Harold R; Noben-Trauth, Konrad

    2011-05-01

    Progressive sensorineural hearing loss in humans is a common and debilitating impairment. Sensorineural deafness in inbred strains of mice is a similarly common and genetically diverse phenotype providing experimental models to study the underlying genetics and the biological effects of the risk factors. Here, we report that ALR/LtJ mice develop early-onset profound sensorineural hearing loss as evidenced by high-to-low frequency hearing threshold shifts, absent distortion-product otoacoustic emissions, and normal endocochlear potentials. Linkage analyses of a segregating backcross revealed three novel quantitative trait loci named sensorineural hearing loss (Snhl) -2, -3, and -4. The QTLs achieved very high LOD scores with markers on chromosome 1 (Snhl2, LOD: 12), chromosome 6 (Snhl3, LOD: 24) and chromosome 10 (Snhl4, LOD: 11). Together, they explained 90% of the phenotypic variance. While Snhl2 and Snhl3 affected hearing thresholds across a broad range of test frequencies, Snhl4 caused primarily high-frequency hearing loss. The hearing impairment is accompanied by an organ of Corti patterning defect that is characterized by the ectopic expression of supernumerary outer hair cells organized in rows along the abneural site of the sensory epithelium in the presence of unaltered planar polarity and otherwise normal cochlear duct morphology. Cloning the Snhl2, -3, and -4 genes in the ALR/LtJ mice may provide important genetic and mechanistic insights into the pathology of human progressive sensorineural deafness. PMID:21185929

  9. Dimerumic Acid and Deferricoprogen Activate Ak Mouse Strain Thymoma/Heme Oxygenase-1 Pathways and Prevent Apoptotic Cell Death in 6-Hydroxydopamine-Induced SH-SY5Y Cells.

    PubMed

    Tseng, Wei-Ting; Hsu, Ya-Wen; Pan, Tzu-Ming

    2016-08-01

    Parkinson's disease (PD) is a neurodegenerative disorder, which can be modeled using the neurotoxin 6-hydroxydopamine (6-OHDA) to generate oxidative stress. Here, we studied the effects of the antioxidants deferricoprogen (DFC) and dimerumic acid (DMA), produced by rice fermented with Monascus purpureus NTU 568, on 6-OHDA-induced apoptosis in SH-SY5Y cells and their potential protective mechanisms. DMA and DFC inhibited 6-OHDA-induced apoptosis and cellular reactive oxygen species (ROS) in SH-SY5Y human neuroblastoma cells. Molecular analysis demonstrated associated upregulation of the Ak mouse strain thymoma (Akt), heme oxygenase-1 (HO-1), and signal-regulated kinase (ERK) pathways along with inhibited phosphorylation of c-Jun N-terminal kinase (JNK) and p38 pathways and altered homodimeric glycoprotein, N-methyl-d-aspartate (NMDA) receptor, and immunoglobulin Fc receptor gene expression. These results suggested that the neuroprotection elicited by DMA and DFC against 6-OHDA-induced neurotoxicity was associated with the Akt, MAPK, and HO-1 pathways via regulating the gene expression of NMDA receptor, homodimeric glycoprotein, and immunoglobulin Fc receptor. PMID:27431098

  10. Subclinical Chlamydial Infection of the Female Mouse Genital Tract Generates a Potent Protective Immune Response: Implications for Development of Live Attenuated Chlamydial Vaccine Strains

    PubMed Central

    Su, Hua; Messer, Ronald; Whitmire, William; Hughes, Scott; Caldwell, Harlan D.

    2000-01-01

    Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed. CD4+ T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection. Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa. Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C. trachomatis vaccine. Attenuated strains of C. trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection. We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection. Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log10) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae. Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice. Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally. These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response. They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs. PMID:10603387

  11. Exercise Capacity and Response to Training Quantitative Trait Loci in a NZW X 129S1 Intercross and Combined Cross Analysis of Inbred Mouse Strains

    PubMed Central

    Massett, Michael P.; Avila, Joshua J.; Kim, Seung Kyum

    2015-01-01

    Genetic factors determining exercise capacity and the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with exercise training in mice. Based on marked differences in training responses in inbred NZW (-0.65 ± 1.73 min) and 129S1 (6.18 ± 3.81 min) mice, a reciprocal intercross breeding scheme was used to generate 285 F2 mice. All F2 mice completed an exercise performance test before and after a 4-week treadmill running program, resulting in an increase in exercise capacity of 1.54 ± 3.69 min (range = -10 to +12 min). Genome-wide linkage scans were performed for pre-training, post-training, and change in run time. For pre-training exercise time, suggestive QTL were identified on Chromosomes 5 (57.4 cM, 2.5 LOD) and 6 (47.8 cM, 2.9 LOD). A significant QTL for post-training exercise capacity was identified on Chromosome 5 (43.4 cM, 4.1 LOD) and a suggestive QTL on Chromosomes 1 (55.7 cM, 2.3 LOD) and 8 (66.1 cM, 2.2 LOD). A suggestive QTL for the change in run time was identified on Chromosome 6 (37.8 cM, 2.7 LOD). To identify shared QTL, this data set was combined with data from a previous F2 cross between B6 and FVB strains. In the combined cross analysis, significant novel QTL for pre-training exercise time and change in exercise time were identified on Chromosome 12 (54.0 cM, 3.6 LOD) and Chromosome 6 (28.0 cM, 3.7 LOD), respectively. Collectively, these data suggest that combined cross analysis can be used to identify novel QTL and narrow the confidence interval of QTL for exercise capacity and responses to training. Furthermore, these data support the use of larger and more diverse mapping populations to identify the genetic basis for exercise capacity and responses to training. PMID:26710100

  12. Training pathologists in mouse pathology.

    PubMed

    Sundberg, J P; Ward, J M; HogenEsch, H; Nikitin, A Yu; Treuting, P M; Macauley, J B; Schofield, P N

    2012-03-01

    Expertise in the pathology of mice has expanded from traditional regulatory and drug safety screening (toxicologic pathology) primarily performed by veterinary pathologists to the highly specialized area of mouse research pathobiology performed by veterinary and medical pathologists encompassing phenotyping of mutant mice and analysis of research experiments exploiting inbred mouse strains and genetically engineered lines. With increasing use of genetically modified mice in research, mouse pathobiology and, by extension, expert mouse research-oriented pathologists have become integral to the success of basic and translational biomedical research. Training for today's research-oriented mouse pathologist must go beyond knowledge of anatomic features of mice and strain-specific background diseases to the specialized genetic nomenclature, husbandry, and genetics, including the methodology of genetic engineering and complex trait analysis. While training can be accomplished through apprenticeships in formal programs, these are often heavily service related and do not provide the necessary comprehensive training. Specialty courses and short-term mentoring with expert specialists are opportunities that, when combined with active practice and publication, will lead to acquisition of the skills required for cutting-edge mouse-based experimental science. PMID:20817889

  13. Mapping of the antibody and T cell recognition profiles of the HN domain (residues 449-859) of the heavy chain of botulinum neurotoxin A in two high-responder mouse strains.

    PubMed

    Dolimbek, Gulnoz S; Dolimbek, Behzod Z; Aoki, K Roger; Atassi, M Zouhair

    2005-01-01

    Using a set of synthetic overlapping peptides, encompassing the entire N-terminal domain (HN,) of the heavy (H) chain of botulinum neurotoxin serotype A (BoNT/A), we have mapped on HN, the regions recognized by Abs (B cells) and by T cells in two inbred mouse strains. After one BoNT/A toxoid injection, BALB/c T cells mounted a weak in vitro response to a region within overlap 687-705/701-719. The remaining peptides stimulated no detectable responses. After 3 injections, BALB/c T cells gave stronger responses to an expanded region within the overlap 687-705/701-719/715-733, peaking at 701-719. BoNT/A-primed BALB/c T cells showed substantial cross-reaction with BoNT/B but did not respond to TeNT. Unlike BALB/c T cells, BoNT/A-primed T cells of SJL cross-reacted well with both BoNT/B and with TeNT. They also recognized a lager epitope profile than the corresponding BALB/c T cells. After one injection with BoNT/A toxoid, SJL T cells responded in vitro to a number of the HN peptides. Regions within peptides 617-635 and 561-579 stimulated strong in vitro responses. Several peptides (463-481, 589-607, 659-677, 729-747, 827-845, and 841-859 revoked weak-to-medium proliferative activities. Four other peptides stimulated very low bu reproducible responses (SI between 2.0 and 3.0). After 3 BoNT/A injections, SJL T cells responded in vitro strongly to peptides 463-481, 561-579, 617-635, 743-761, and 841-859. There were medium or weak responses to at least 10 other peptides. The cells also responded well to the L-chain peptide 218-231. Antisera of BALB/c and SJL obtained after 3 injections with BoNT/A toxoid, protected at very high dilution recipient mice against LD105 of BoNT/A. BALB/c Abs showed medium-to-high binding to peptides 533-551/547-565, 785-803, and 813-831/827-845. Four other peptides showed very low binding. The corresponding SJL Abs had high binding to the overlap 533-551/547-565/561-579, and peptides 743-761, 785-803, and 813-831. Thre other peptides bound low

  14. Natural Strain

    NASA Technical Reports Server (NTRS)

    Freed, Alan D.

    1997-01-01

    Logarithmic strain is the preferred measure of strain used by materials scientists, who typically refer to it as the "true strain." It was Nadai who gave it the name "natural strain," which seems more appropriate. This strain measure was proposed by Ludwik for the one-dimensional extension of a rod with length l. It was defined via the integral of dl/l to which Ludwik gave the name "effective specific strain." Today, it is after Hencky, who extended Ludwik's measure to three-dimensional analysis by defining logarithmic strains for the three principal directions.

  15. Mouse Genome Database: from sequence to phenotypes and disease models

    PubMed Central

    Eppig, Janan T.; Richardson, Joel E.; Kadin, James A.; Smith, Cynthia L.; Blake, Judith A.; Bult, Carol J.

    2015-01-01

    The Mouse Genome Database (MGD, www.informatics.jax.org) is the international scientific database for genetic, genomic, and biological data on the laboratory mouse to support the research requirements of the biomedical community. To accomplish this goal, MGD provides broad data coverage, serves as the authoritative standard for mouse nomenclature for genes, mutants, and strains, and curates and integrates many types of data from literature and electronic sources. Among the key data sets MGD supports are: the complete catalog of mouse genes and genome features, comparative homology data for mouse and vertebrate genes, the authoritative set of Gene Ontology (GO) annotations for mouse gene functions, a comprehensive catalog of mouse mutations and their phenotypes, and a curated compendium of mouse models of human diseases. Here we describe the data acquisition process, specifics about MGD’s key data areas, methods to access and query MGD data, and outreach and user help facilities. PMID:26150326

  16. Mouse Genome Database: From sequence to phenotypes and disease models.

    PubMed

    Eppig, Janan T; Richardson, Joel E; Kadin, James A; Smith, Cynthia L; Blake, Judith A; Bult, Carol J

    2015-08-01

    The Mouse Genome Database (MGD, www.informatics.jax.org) is the international scientific database for genetic, genomic, and biological data on the laboratory mouse to support the research requirements of the biomedical community. To accomplish this goal, MGD provides broad data coverage, serves as the authoritative standard for mouse nomenclature for genes, mutants, and strains, and curates and integrates many types of data from literature and electronic sources. Among the key data sets MGD supports are: the complete catalog of mouse genes and genome features, comparative homology data for mouse and vertebrate genes, the authoritative set of Gene Ontology (GO) annotations for mouse gene functions, a comprehensive catalog of mouse mutations and their phenotypes, and a curated compendium of mouse models of human diseases. Here, we describe the data acquisition process, specifics about MGD's key data areas, methods to access and query MGD data, and outreach and user help facilities. PMID:26150326

  17. Natural Strain

    NASA Technical Reports Server (NTRS)

    Freed, Alan D.

    1995-01-01

    The purpose of this paper is to present a consistent and thorough development of the strain and strain-rate measures affiliated with Hencky. Natural measures for strain and strain-rate, as I refer to them, are first expressed in terms of of the fundamental body-metric tensors of Lodge. These strain and strain-rate measures are mixed tensor fields. They are mapped from the body to space in both the Eulerian and Lagrangian configurations, and then transformed from general to Cartesian fields. There they are compared with the various strain and strain-rate measures found in the literature. A simple Cartesian description for Hencky strain-rate in the Lagrangian state is obtained.

  18. The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

    PubMed

    Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

    2015-01-01

    The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. PMID:25348401

  19. Cellular Genes in the Mouse Regulate IN TRANS the Expression of Endogenous Mouse Mammary Tumor Viruses

    PubMed Central

    Traina-Dorge, Vicki L.; Carr, Jean K.; Bailey-Wilson, Joan E.; Elston, Robert C.; Taylor, Benjamin A.; Cohen, J. Craig

    1985-01-01

    The transcriptional activities of the eleven mouse mammary tumor virus (MMTV) proviruses endogenous to two sets of recombinant inbred (RI) mouse strains, BXD and BXH, were characterized. Comparison of the levels of virus-specific RNA quantitated in each strain showed no direct relationship between the presence of a particular endogenous provirus or with increasing numbers of proviruses. Association of specific genetic markers with the level of MMTV-specific RNA was examined by using multiple regression analysis. Several cellular loci as well as proviral loci were identified that were significantly associated with viral expression. Importantly, these cellular loci associated with MMTV expression segregated independently of viral sequences. PMID:2996982

  20. Human prion strain selection in transgenic mice

    PubMed Central

    Giles, Kurt; Glidden, David V.; Patel, Smita; Korth, Carsten; Groth, Darlene; Lemus, Azucena; DeArmond, Stephen J.; Prusiner, Stanley B.

    2010-01-01

    Transgenic (Tg) mice expressing chimeras of mouse and human prion proteins (PrP) have shorter incubation periods for Creutzfeldt-Jakob disease (CJD) prions than mice expressing full-length human PrP. Increasing the sequence similarity of the chimeric PrP to mouse PrP, by reverting human residues to mouse, resulted in a Tg line, denoted Tg22372, which was susceptible to sporadic (s) CJD prions in ~110 days 1. Reversion of one additional residue (M111V) resulted in a new Tg line, termed Tg1014, susceptible to sCJD prions in ~75 days. Tg1014 mice also has shorter incubation periods for variant (v) CJD prions, providing a more tractable model for studying this prion strain. Transmission of vCJD prions to Tg1014 mice resulted in two different strains, determined by neuropathology and biochemical analysis, which correlated with the length of the incubation time. One strain had the biochemical, neuropathological, and transmission characteristics including longer incubation times of the inoculated vCJD strain; the second strain produced a phenotype resembling that of sCJD prions including relatively shorter incubation periods. Mice with intermediate incubation periods for vCJD prions had a mixture of the two strains. Both strains were serially transmitted in Tg1014 mice, which led to further reduction in incubation periods. Conversion of vCJD-like to sCJD-like strains was favored in Tg1014 mice more than in the Tg22372 line. The single amino acid difference therefore appears to offer selective pressure for propagation of the sCJD-like strain. These two Tg mouse lines provide relatively rapid models to study human prion diseases as well as the evolution of human prion strains. PMID:20695008

  1. Integration of Mouse Phenome Data Resources

    SciTech Connect

    Hancock, John M; Adams, Neils; Aidinis, Vassilis; Blake, Judith A; Bogue, Molly; Brown, Steve D M; Chesler, Elissa J; Davidson, Duncan; Duran, Christopher; Eppig, Janan T; Gailus-Durner, Valerie; Gkoutos, Georgios V; Greenaway, Simon; Angelis, Martin Hrabe de; Kollias, George; Leblanc, Sophie; Lee, Kirsty; Lengger, Christoph; Maier, Holger; Mallon, Ann-Marie; Masuya, Hiroshi; Melvin, David; Muller, Werner; Parkinson, Helen; Proctor, Glenn; Reuveni, Eli; Schofield, Paul; Shukla, Aadya; Smith, Cynthia; Toyoda, Tetsuro; Vasseur, Laurent; Wakana, Shigeharu; Walling, Alison; White, Jacqui; Wood, Joe; Zouberakis, Michalis

    2008-01-01

    Understanding the functions encoded in the mouse genome will be central to an understanding of the genetic basis of human disease. To achieve this it will be essential to be able to characterise the phenotypic consequences of variation and alterations in individual genes. Data on the phenotypes of mouse strains are currently held in a number of different forms (detailed descriptions of mouse lines, first line phenotyping data on novel mutations, data on the normal features of inbred lines, etc.) at many sites worldwide. For the most efficient use of these data sets, we have set in train a process to develop standards for the description of phenotypes (using ontologies), and file formats for the description of phenotyping protocols and phenotype data sets. This process is ongoing, and needs to be supported by the wider mouse genetics and phenotyping communities to succeed. We invite interested parties to contact us as we develop this process further.

  2. A catalog of the mouse gut metagenome.

    PubMed

    Xiao, Liang; Feng, Qiang; Liang, Suisha; Sonne, Si Brask; Xia, Zhongkui; Qiu, Xinmin; Li, Xiaoping; Long, Hua; Zhang, Jianfeng; Zhang, Dongya; Liu, Chuan; Fang, Zhiwei; Chou, Joyce; Glanville, Jacob; Hao, Qin; Kotowska, Dorota; Colding, Camilla; Licht, Tine Rask; Wu, Donghai; Yu, Jun; Sung, Joseph Jao Yiu; Liang, Qiaoyi; Li, Junhua; Jia, Huijue; Lan, Zhou; Tremaroli, Valentina; Dworzynski, Piotr; Nielsen, H Bjørn; Bäckhed, Fredrik; Doré, Joël; Le Chatelier, Emmanuelle; Ehrlich, S Dusko; Lin, John C; Arumugam, Manimozhiyan; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2015-10-01

    We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies. PMID:26414350

  3. Multimodal, multidimensional models of mouse brain.

    PubMed

    Mackenzie-Graham, Allan J; Lee, Erh-Fang; Dinov, Ivo D; Yuan, Heng; Jacobs, Russell E; Toga, Arthur W

    2007-01-01

    Naturally occurring mutants and genetically manipulated strains of mice are widely used to model a variety of human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison and to facilitate the integration of anatomic, genetic, and physiologic observations from multiple subjects and experiments. We have developed digital atlases of the C57BL/6J mouse brain (adult and neonate) as comprehensive frameworks for storing and accessing the myriad types of information about the mouse brain. Along with raw and annotated images, these contain database management systems and a set of tools for comparing information from different techniques and different animals. Each atlas establishes a canonical representation of the mouse brain and provides the tools for the manipulation and analysis of new data. We describe both these atlases and discuss how they may be put to use in organizing and analyzing data from mouse models of epilepsy. PMID:17767578

  4. Reciprocal virulence and resistance polymorphism in the relationship between Toxoplasma gondii and the house mouse

    PubMed Central

    Lilue, Jingtao; Müller, Urs Benedikt; Steinfeldt, Tobias; Howard, Jonathan C

    2013-01-01

    Virulence in the ubiquitous intracellular protozoon Toxoplasma gondii for its natural intermediate host, the mouse, appears paradoxical from an evolutionary standpoint because death of the mouse before encystment interrupts the parasite life cycle. Virulent T. gondii strains secrete kinases and pseudokinases that inactivate the immunity-related GTPases (IRG proteins) responsible for mouse resistance to avirulent strains. Such considerations stimulated a search for IRG alleles unknown in laboratory mice that might confer resistance to virulent strains of T. gondii. We report that the mouse IRG system shows extraordinary polymorphic complexity in the wild. We describe an IRG haplotype from a wild-derived mouse strain that confers resistance against virulent parasites by interference with the virulent kinase complex. In such hosts virulent strains can encyst, hinting at an explanation for the evolution of virulence polymorphism in T. gondii. DOI: http://dx.doi.org/10.7554/eLife.01298.001 PMID:24175088

  5. Strain Gage

    NASA Technical Reports Server (NTRS)

    1995-01-01

    HITEC Corporation developed a strain gage application for DanteII, a mobile robot developed for NASA. The gage measured bending forces on the robot's legs and warned human controllers when acceptable forces were exceeded. HITEC further developed the technology for strain gage services in creating transducers out of "Indy" racing car suspension pushrods, NASCAR suspension components and components used in motion control.

  6. IDENTIFICATION OF STEROCHEMICAL CONFIGERATION OF CYCLOPENTA[CD]PYRENE-DNA ADDUCTS IN STRAIN A/J MOUSE LUNG AND C3H10T1/2CL8

    EPA Science Inventory

    The definitive identification of stereochemical configurations of DNA adducts detected by 32P-postlabeling requires co-chromatography of adducts with synthetic chromatographic standards. Four major and several minor DNA adducts are formed by cyclopenta[cd]pyrene (CPP) in strain A...

  7. Involvement of the 5-HT(1A) receptor in the anti-immobility effects of fluvoxamine in the forced swimming test and mouse strain differences in 5-HT(1A) receptor binding.

    PubMed

    Sugimoto, Yumi; Furutani, Sachiko; Kajiwara, Yoshinobu; Hirano, Kazufumi; Yamada, Shizuo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hotta, Yoshihiro; Yamada, Jun

    2010-03-10

    We previously demonstrated the presence of strain differences in baseline immobility time and sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine in five strains of mice (ICR, ddY, C57BL, DBA/2 and BALB/c mice). Furthermore, variations in serotonin (5-HT) transporter binding in the brain were strongly related to strain differences in baseline immobility and sensitivity to fluvoxamine. In the present study, we examined the involvement of the 5-HT(1A) receptor in anti-immobility effects in DBA/2 mice, which show high sensitivity to fluvoxamine. The anti-immobility effects of fluvoxamine in DBA/2 mice were inhibited by the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). However, the 5-HT(1B) receptor antagonist 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide (GR55562), the 5-HT(2) receptor antagonist 6-methyl-1-(methylethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY 53857), the 5-HT(3) receptor antagonist ondansetron and the 5-HT(4) receptor antagonist 4-amino-5-chloro-2-methoxy-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205,557) did not influence the anti-immobility effects of fluvoxamine in DBA/2 mice. These results suggest that fluvoxamine-induced antidepressant-like effects in DBA/2 mice are mediated by the 5-HT(1A) receptor. We analyzed 5-HT(1A) receptor binding in the brains of five strains of mice. Strain differences in 5-HT(1A) receptor binding were observed. 5-HT(1A) receptor binding in brain was not correlated with baseline immobility time in the five strains of mice examined. These results suggest that, although the anti-immobility effects of fluvoxamine in DBA/2 mice are mediated by the 5-HT(1A) receptor, strain differences in 5-HT(1A) receptor binding are not related to variation in immobility time and responses to fluvoxamine. PMID:19958758

  8. The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease

    PubMed Central

    Eppig, Janan T.; Blake, Judith A.; Bult, Carol J.; Kadin, James A.; Richardson, Joel E.

    2015-01-01

    The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse–human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human–Mouse: Disease Connection, allows users to explore gene–phenotype–disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. PMID:25348401

  9. Genetically Engineered Mouse Models for Studying Inflammatory Bowel Disease

    PubMed Central

    Mizoguchi, Atsushi; Takeuchi, Takahito; Himuro, Hidetomo; Okada, Toshiyuki; Mizoguchi, Emiko

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. PMID:26387641

  10. A Mouse Strain Defective in Both T Cells and NK Cells Has Enhanced Sensitivity to Tumor Induction by Plasmid DNA Expressing Both Activated H-Ras and c-Myc

    PubMed Central

    Sheng-Fowler, Li; Tu, Wei; Fu, Haiqing; Murata, Haruhiko; Lanning, Lynda; Foseh, Gideon; Macauley, Juliete; Blair, Donald; Hughes, Stephen H.; Coffin, John M.; Lewis, Andrew M.; Peden, Keith

    2014-01-01

    As part of safety studies to evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cells, we have been developing in vivo assays to detect and quantify the oncogenic activity of DNA. We generated a plasmid expressing both an activated human H-ras gene and murine c-myc gene and showed that 1 µg of this plasmid, pMSV-T24-H-ras/MSV-c-myc, was capable of inducing tumors in newborn NIH Swiss mice. However, to be able to detect the oncogenicity of dominant activated oncogenes in cellular DNA, a more sensitive system was needed. In this paper, we demonstrate that the newborn CD3 epsilon transgenic mouse, which is defective in both T-cell and NK-cell functions, can detect the oncogenic activity of 25 ng of the circular form of pMSV-T24-H-ras/MSV-c-myc. When this plasmid was inoculated as linear DNA, amounts of DNA as low as 800 pg were capable of inducing tumors. Animals were found that had multiple tumors, and these tumors were independent and likely clonal. These results demonstrate that the newborn CD3 epsilon mouse is highly sensitive for the detection of oncogenic activity of DNA. To determine whether it can detect the oncogenic activity of cellular DNA derived from four human tumor-cell lines (HeLa, A549, HT-1080, and CEM), DNA (100 µg) was inoculated into newborn CD3 epsilon mice both in the presence of 1 µg of linear pMSV-T24-H-ras/MSV-c-myc as positive control and in its absence. While tumors were induced in 100% of mice with the positive-control plasmid, no tumors were induced in mice receiving any of the tumor DNAs alone. These results demonstrate that detection of oncogenes in cellular DNA derived from four human tumor-derived cell lines in this mouse system was not possible; the results also show the importance of including a positive-control plasmid to detect inhibitory effects of the cellular DNA. PMID:25302710

  11. Host genetic and environmental effects on mouse intestinal microbiota

    PubMed Central

    Campbell, James H; Foster, Carmen M; Vishnivetskaya, Tatiana; Campbell, Alisha G; Yang, Zamin K; Wymore, Ann; Palumbo, Anthony V; Chesler, Elissa J; Podar, Mircea

    2012-01-01

    The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel. PMID:22695862

  12. Host Genetic and Environmental Effects on Mouse Cecum Microbiota

    SciTech Connect

    Campbell, James H; Foster, Carmen M; Vishnivetskaya, Tatiana A; Campbell, Alisha G; Yang, Zamin Koo; Wymore, Ann; Palumbo, Anthony Vito; Podar, Mircea

    2012-01-01

    The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.

  13. Mouse Curve Biometrics

    SciTech Connect

    Schulz, Douglas A.

    2007-10-08

    A biometric system suitable for validating user identity using only mouse movements and no specialized equipment is presented. Mouse curves (mouse movements with little or no pause between them) are individually classied and used to develop classication histograms, which are representative of an individual's typical mouse use. These classication histograms can then be compared to validate identity. This classication approach is suitable for providing continuous identity validation during an entire user session.

  14. Optical mouse acting as biospeckle sensor

    NASA Astrophysics Data System (ADS)

    da Silva, Michel Melo; Nozela, Jose Roberto de Almeida; Chaves, Marcio Jose; Alves Braga, Roberto; Rabal, Hector Jorge

    2011-04-01

    In this work we propose some experiments with the use of optical computer mouse, associated to low cost lasers that can be used to perform several measurements with applications in industry and in human health monitoring. The mouse was used to grab the movements produced by speckle pattern changes and to get information through the adaptation of its structure. We measured displacements in wood samples under strain, variations of the diameter of an artery due to heart beat and, through a hardware simulation, the movement of an eye, an experiment that could be of low cost help for communication to severely handicapped motor patients. Those measurements were done in spite of the fact that the CCD sensor of the mice is monolithically included into an integrated circuit so that the raw image cannot be accessed. If, as was the case with primitive optical mouse, that signal could be accessed, the quality and usefulness of the measurements could be significantly increased. As it was not possible, a webcam sensor was used for measuring the drying of paint, a standard phenomenon for testing biospeckle techniques, in order to prove the usefulness of the mouse design. The results showed that the use of the mouse associated to a laser pointer could be the way to get metrological information from many phenomena involving the whole field spatial displacement, as well as the use of the mouse as in its prime version allowed to get images of the speckle patterns and to analyze them.

  15. Building a Brainier Mouse.

    ERIC Educational Resources Information Center

    Tsien, Joe Z.

    2000-01-01

    Describes a genetic engineering project to build an intelligent mouse. Cites understanding the molecular basis of learning and memory as a very important step. Concludes that while science will never create a genius mouse that plays the stock market, it can turn a mouse into a quick learner with a better memory. (YDS)

  16. INFRAFRONTIER—providing mutant mouse resources as research tools for the international scientific community

    PubMed Central

    2015-01-01

    The laboratory mouse is a key model organism to investigate mechanism and therapeutics of human disease. The number of targeted genetic mouse models of disease is growing rapidly due to high-throughput production strategies employed by the International Mouse Phenotyping Consortium (IMPC) and the development of new, more efficient genome engineering techniques such as CRISPR based systems. We have previously described the European Mouse Mutant Archive (EMMA) resource and how this international infrastructure provides archiving and distribution worldwide for mutant mouse strains. EMMA has since evolved into INFRAFRONTIER (http://www.infrafrontier.eu), the pan-European research infrastructure for the systemic phenotyping, archiving and distribution of mouse disease models. Here we describe new features including improved search for mouse strains, support for new embryonic stem cell resources, access to training materials via a comprehensive knowledgebase and the promotion of innovative analytical and diagnostic techniques. PMID:25414328

  17. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercaria- I. analysis of antibody and T-lymphocyte responses in mouse strains developing differing levels of immunity

    SciTech Connect

    James, S.L.; Labine, M.; Sher, A.

    1981-11-15

    The kinetics of cellular and humoral responses directed against schistosomula were examined in mice of three inbred strains which demonstrate differences in the degree of resistance induced by immunization with irradiated cercariae. T-Cell reactivity was observed during the first 4 weeks after vaccination but declined to control levels thereafter. Anti-schistosomulum antibody was first detected 2 weeks after vaccination, peaked by 6 weeks, and persisted as late as 15 weeks. In sera obtained at 6 weeks, antibody activity was detected in affinity chromatography-purified fractions containing IgM, IgA, IgG/sub 1/, IgG/sub 2//sub a/, and IgG/sub 3/ immunoglobulins. In general, the cellular and humoral responses observed in C57Bl/6J mice, which consistently developed a high level of immunity after vaccination, were not significantly different from those observed in C3H/HeJ or CBA/J mice, which achieved only low to moderate levels of immunity. Thus, although antibody production appears to correlate more closely than T lymphocyte responsiveness with the typical long-term resistance pattern observed in this model, the absence of striking differences in parasite-specific antibody levels between mice of these different strains suggests that additional mechanisms may be involved in the development of immunity after vaccination.

  18. Evaluation of atlas based mouse brain segmentation

    NASA Astrophysics Data System (ADS)

    Lee, Joohwi; Jomier, Julien; Aylward, Stephen; Tyszka, Mike; Moy, Sheryl; Lauder, Jean; Styner, Martin

    2009-02-01

    Magentic Reasonance Imaging for mouse phenotype study is one of the important tools to understand human diseases. In this paper, we present a fully automatic pipeline for the process of morphometric mouse brain analysis. The method is based on atlas-based tissue and regional segmentation, which was originally developed for the human brain. To evaluate our method, we conduct a qualitative and quantitative validation study as well as compare of b-spline and fluid registration methods as components in the pipeline. The validation study includes visual inspection, shape and volumetric measurements and stability of the registration methods against various parameter settings in the processing pipeline. The result shows both fluid and b-spline registration methods work well in murine settings, but the fluid registration is more stable. Additionally, we evaluated our segmentation methods by comparing volume differences between Fmr1 FXS in FVB background vs C57BL/6J mouse strains.

  19. Mouse embryonic stem cells with a multi-integrase mouse artificial chromosome for transchromosomic mouse generation.

    PubMed

    Yoshimura, Yuki; Nakamura, Kazuomi; Endo, Takeshi; Kajitani, Naoyo; Kazuki, Kanako; Kazuki, Yasuhiro; Kugoh, Hiroyuki; Oshimura, Mitsuo; Ohbayashi, Tetsuya

    2015-08-01

    The mouse artificial chromosome (MAC) has several advantages as a gene delivery vector, including stable episomal maintenance of the exogenous genetic material and the ability to carry large and/or multiple gene inserts including their regulatory elements. Previously, a MAC containing multi-integration site (MI-MAC) was generated to facilitate transfer of multiple genes into desired cells. To generate transchromosomic (Tc) mice containing a MI-MAC with genes of interest, the desired genes were inserted into MI-MAC in CHO cells, and then the MI-MAC was transferred to mouse embryonic stem (mES) cells via microcell-mediated chromosome transfer (MMCT). However, the efficiency of MMCT from CHO to mES cells is very low (<10(-6)). In this study, we constructed mES cell lines containing a MI-MAC vector to directly insert a gene of interest into the MI-MAC in mES cells via a simple transfection method for Tc mouse generation. The recombination rate of the GFP gene at each attachment site (FRT, PhiC31attP, R4attP, TP901-1attP and Bxb1attP) on MI-MAC was greater than 50% in MI-MAC mES cells. Chimeric mice with high coat colour chimerism were generated from the MI-MAC mES cell lines and germline transmission from the chimera was observed. As an example for the generation of Tc mice with a desired gene by the MI-MAC mES approach, a Tc mouse strain ubiquitously expressing Emerald luciferase was efficiently established. Thus, the findings suggest that this new Tc strategy employing mES cells and a MI-MAC vector is efficient and useful for animal transgenesis. PMID:26055730

  20. 2,3,7,8-Tetrachlorodibenzo-p-dioxin causes increases in expression of c-erb-A and levels of protein-tyrosine kinases in selected tissues of responsive mouse strains

    SciTech Connect

    Bombick, D.W.; Jankun, J.; Tullis, K.; Matsumura, F. )

    1988-06-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) administered in vivo causes drastic reduction in the weight of the mouse thymus at low doses the reduction becoming statistically significant after 2 days. To understand the cause for such thymic involution TCDD-evoked changes in various biochemical parameters in this tissue were examined. The most noticeable change was observed in the increased activity of specific protein-tyrosine kinases and protein kinase C and an increased level of p21{sup ras}-associated binding of ({sup 3}H)GTP. The above changes appear to be a selective effect on these special classes of proteins. It has become apparent that the rise in protein-tyrosine kinase activities becomes significant within 24 hr, whereas the rise in protein kinase C does not become significant until 48 hr. In view of similarities between TCDD and thyroid hormones in causing thymic involution, the levels of c-erb-A expression were assessed in the liver by using avian {sup 32}P-labeled v-erb-A probe and RNA transfer blot hybridization technique. The results clearly indicate that TCDD has the property to elevate levels of mRNA bearing homology to v-erb-A. Based on such observations a hypothesis has been proposed that TCDD owes its potency to its ability to stimulate the expression of one of a family of DNAs bearing homology to v-erb-A and that one of the major consequences of such an action is stimulation of various tyrosine kinases.

  1. Pathology of Mouse Models of Accelerated Aging.

    PubMed

    Harkema, L; Youssef, S A; de Bruin, A

    2016-03-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data. PMID:26864891

  2. Group V Secretory Phospholipase A2 Amplifies the Induction of Cyclooxygenase 2 and Delayed Prostaglandin D2 Generation in Mouse Bone Marrow Culture-Derived Mast Cells in a Strain-Dependent Manner.

    PubMed Central

    Diaz, Bruno L.; Satake, Yoshiyuki; Kikawada, Eriya; Balestrieri, Barbara; Arm, Jonathan P.

    2006-01-01

    Activation of bone marrow-derived mast cells (BMMC) with stem cell factor (SCF) or IgE and antigen elicits exocytosis and an immediate phase of prostaglandin (PG) D2 and leukotriene (LT) C4 generation. Activation of BMMC by SCF, IL-1β and IL-10 elicits a delayed phase of PGD2 generation dependent on cyclooxygenase (COX) 2 induction. Cytosolic phospholipase A2 α provides arachidonic acid in both phases and amplifies COX-2 induction. Pharmacological experiments implicate an amplifying role for secretory (s) PLA2. We used mice lacking the gene encoding group V sPLA2 (Pla2g5 −/−) to definitively test its role in eicosanoid generation by BMMC. Pla2g5 −/− BMMC on a C57BL/6 genetic background showed a modest reduction in exocytosis and immediate PGD2 generation after activation with SCF or with IgE and antigen, while LTC4 generation was not modified. Delayed-phase PGD2 generation and COX-2 induction were reduced ~35% in C57BL/6 Pla2g5 −/− BMMC and were restored by exogenous PGE2. There was no deficit in either phase of eicosanoid generation by Pla2g5 −/− BMMC on a BALB/c background. Thus, group V sPLA2 amplifies COX-2 expression and delayed phase PGD2 generation in a strain-dependent manner; it has at best a limited role in immediate eicosanoid generation by BMMC. PMID:17064958

  3. Genetic characterization of senescence-accelerated mouse (SAM).

    PubMed

    Higuchi, K

    1997-01-01

    The Senescence-Accelerated Mouse (SAM) strains are unique and appropriate models for genetic studies on aging because the SAMP strains have an "accelerated senescence" phenotype for which the SAMR strains are controls, and each SAMP strain has a strain-specific age-associated disorder. Furthermore, because they have gone through sufficient generations of sister-brother mating, they can be considered inbred strains, which can be analyzed genetically. There are now 11 SAMP strains and 3 SAMR strains descended from the progenitor litters. Analysis with the Gompertz function shows that the SAMP strains have the same initial mortality rate (IMR) as the SAMR strains but a shorter mortality rate doubling time (MRDT), presumably due to genes that accelerated the rate of senescence in the SAMP strains. This accelerated senescence may also occur in cultured fibroblast-like cells. We performed molecular genetic characterization of all the SAM strains to acquire a base of genetic information from which we could develop hypotheses on the mechanism of development of SAM strains and genetic factors that contribute to accelerated senescence. PMID:9088910

  4. Hip flexor strain - aftercare

    MedlinePlus

    Pulled hip flexor - aftercare; Hip flexor injury - aftercare; Hip flexor tear - aftercare; Iliopsoas strain - aftercare; Strained iliopsoas muscle - aftercare; Torn iliopsoas muscle - aftercare; Psoas strain - aftercare

  5. Prion infection of mouse neurospheres

    PubMed Central

    Giri, Ranjit K.; Young, Rebecca; Pitstick, Rose; DeArmond, Stephen J.; Prusiner, Stanley B.; Carlson, George A.

    2006-01-01

    Only a few cell lines have been infected with prions, offering limited genetic diversity and sensitivity to several strains. Here we report that cultured neurospheres expressing cellular prion protein (PrPC) can be infected with prions. Neurosphere lines isolated from the brains of mice at embryonic day 13–15 grow as aggregates and contain CNS stem cells. We produced neurosphere cultures from FVB/NCr (FVB) mice, from transgenic (Tg) FVB mice that overexpress mouse PrP-A (Tg4053), and from congenic FVB mice with a targeted null mutation in the PrP gene (Prnp0/0) and incubated them with the Rocky Mountain Laboratory prion strain. While monitoring the levels of disease-causing PrP (PrPSc) at each passage, we observed a dramatic rise in PrPSc levels with time in the Tg4053 neurosphere cells, whereas the level of PrPSc decayed to undetectable levels in cell cultures lacking PrP. PrPSc levels in cultures from FVB mice initially declined but then increased with passage. Prions produced in culture were transmissible to mice and produced disease pathology. Intracellular aggregates of PrPSc were present in cells from infected cultures. The susceptibility of neurosphere cultures to prions mirrored that of the mice from which they were derived. Neurosphere lines from Tg4053 mice provide a sensitive in vitro bioassay for mouse prions; neurosphere lines from other Tg mice overexpressing PrP might be used to assay prions from other species, including humans. PMID:16495413

  6. Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse.

    PubMed

    Petkov, Petko M; Cassell, Megan A; Sargent, Evelyn E; Donnelly, Charles J; Robinson, Phil; Crew, Victor; Asquith, Steven; Haar, Raymond Vonder; Wiles, Michael V

    2004-05-01

    We have developed a genotyping system for detecting genetic contamination in the laboratory mouse based on assaying single-nucleotide polymorphism (SNP) markers positioned on all autosomes and the X chromosome. This system provides a fast, reliable, and cost-effective way for genetic monitoring, while maintaining a very high degree of confidence. We describe the allelic distribution of 235 SNPs in 48 mouse strains, thereby creating a database of polymorphisms useful for genotyping purposes. The SNP markers used in this study were chosen from publicly available SNP databases. Four genotyping methods were evaluated, and dynamic two-tube allele-specific PCR assays were developed for each marker and tested on a set of 48 inbred mouse strains. The minimal number of assays sufficient to distinguish groups consisting of different numbers of mouse strains was estimated, and a panel of 28 SNPs sufficient to distinguish virtually all of the inbred strains tested was selected. Amplifluor SNP detection assays were developed for these markers and tested on an extended list of 96 strains. This panel was used as a genetic quality control approach to monitor the genotypes of nearly 300 inbred, wild-derived, congenic, consomic, and recombinant inbred strains maintained at The Jackson Laboratory. We have concluded that this marker panel is sufficient for genetic contamination monitoring in colonies containing a large number of genetically diverse mouse strains and that reduced versions of the panel could be implemented in facilities housing a lower number of strains. PMID:15081119

  7. The MOUSE Squad

    ERIC Educational Resources Information Center

    Borja, Rhea R.

    2004-01-01

    This article presents a New York city after-school program started by MOUSE (Making Opportunities for Upgrading Schools and Education), a national nonprofit group that teaches students how to fix computers, and equips them with the communication and problem-solving skills to help them in the working world. The MOUSE program is part of a trend…

  8. Mouse genome database 2016

    PubMed Central

    Bult, Carol J.; Eppig, Janan T.; Blake, Judith A.; Kadin, James A.; Richardson, Joel E.

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data. PMID:26578600

  9. Mouse genome database 2016.

    PubMed

    Bult, Carol J; Eppig, Janan T; Blake, Judith A; Kadin, James A; Richardson, Joel E

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data. PMID:26578600

  10. Evaluation of an in vitro toxicogenetic mouse model for hepatotoxicity

    SciTech Connect

    Martinez, Stephanie M.; Bradford, Blair U.; Soldatow, Valerie Y.; Witek, Rafal; Kaiser, Robert; Stewart, Todd; Amaral, Kirsten; Freeman, Kimberly; Black, Chris; LeCluyse, Edward L.; Ferguson, Stephen S.

    2010-12-15

    Numerous studies support the fact that a genetically diverse mouse population may be useful as an animal model to understand and predict toxicity in humans. We hypothesized that cultures of hepatocytes obtained from a large panel of inbred mouse strains can produce data indicative of inter-individual differences in in vivo responses to hepato-toxicants. In order to test this hypothesis and establish whether in vitro studies using cultured hepatocytes from genetically distinct mouse strains are feasible, we aimed to determine whether viable cells may be isolated from different mouse inbred strains, evaluate the reproducibility of cell yield, viability and functionality over subsequent isolations, and assess the utility of the model for toxicity screening. Hepatocytes were isolated from 15 strains of mice (A/J, B6C3F1, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, BALB/cByJ, AKR/J, MRL/MpJ, NOD/LtJ, NZW/LacJ, PWD/PhJ and WSB/EiJ males) and cultured for up to 7 days in traditional 2-dimensional culture. Cells from B6C3F1, C57BL/6J, and NOD/LtJ strains were treated with acetaminophen, WY-14,643 or rifampin and concentration-response effects on viability and function were established. Our data suggest that high yield and viability can be achieved across a panel of strains. Cell function and expression of key liver-specific genes of hepatocytes isolated from different strains and cultured under standardized conditions are comparable. Strain-specific responses to toxicant exposure have been observed in cultured hepatocytes and these experiments open new opportunities for further developments of in vitro models of hepatotoxicity in a genetically diverse population.

  11. Automated measurement of mouse apolipoprotein B: convenient screening tool for mouse models of atherosclerosis.

    PubMed

    Levine, D M; Williams, K J

    1997-04-01

    Although mice are commonly used for studies of atherosclerosis, investigators have had no convenient way to quantify apolipoprotein (apo) B, the major protein of atherogenic lipoproteins, in this model. We now report an automated immunoturbidimetric assay for mouse apo B with an NCCLS imprecision study CV < 5%. Added hemoglobin up to 50 g/L did not interfere with the assay, nor did one freeze-thaw cycle of serum samples. Assay linearity extends to apo B concentrations of 325 mg/L. We have used the assay to determine serum apo B concentrations under several atherogenic conditions, including the apo E "knock-out" genotype and treatment with a high-cholesterol diet. Our assay can be used to survey inbred mouse strains for variants in apo B concentrations or regulation. Moreover, the mouse can now be used as a convenient small-animal model to screen compounds that may lower apo B concentrations. PMID:9105271

  12. Mouse SNP Miner: an annotated database of mouse functional single nucleotide polymorphisms

    PubMed Central

    Reuveni, Eli; Ramensky, Vasily E; Gross, Cornelius

    2007-01-01

    Background The mapping of quantitative trait loci in rat and mouse has been extremely successful in identifying chromosomal regions associated with human disease-related phenotypes. However, identifying the specific phenotype-causing DNA sequence variations within a quantitative trait locus has been much more difficult. The recent availability of genomic sequence from several mouse inbred strains (including C57BL/6J, 129X1/SvJ, 129S1/SvImJ, A/J, and DBA/2J) has made it possible to catalog DNA sequence differences within a quantitative trait locus derived from crosses between these strains. However, even for well-defined quantitative trait loci (<10 Mb) the identification of candidate functional DNA sequence changes remains challenging due to the high density of sequence variation between strains. Description To help identify functional DNA sequence variations within quantitative trait loci we have used the Ensembl annotated genome sequence to compile a database of mouse single nucleotide polymorphisms (SNPs) that are predicted to cause missense, nonsense, frameshift, or splice site mutations (available at ). For missense mutations we have used the PolyPhen and PANTHER algorithms to predict whether amino acid changes are likely to disrupt protein function. Conclusion We have developed a database of mouse SNPs predicted to cause missense, nonsense, frameshift, and splice-site mutations. Our analysis revealed that 20% and 14% of missense SNPs are likely to be deleterious according to PolyPhen and PANTHER, respectively, and 6% are considered deleterious by both algorithms. The database also provides gene expression and functional annotations from the Symatlas, Gene Ontology, and OMIM databases to further assess candidate phenotype-causing mutations. To demonstrate its utility, we show that Mouse SNP Miner successfully finds a previously identified candidate SNP in the taste receptor, Tas1r3, that underlies sucrose preference in the C57BL/6J strain. We also use Mouse

  13. CHARACTERIZATION OF AEROMONAS VIRULENCE USING AN IMMUNOCOMPROMISED MOUSE MODEL

    EPA Science Inventory

    An immunocompromised mouse model was used to characterize Aeromonas strains for their ability to cause opportunistic, extraintestinal infections. A total of 34 isolates of Aeromonas (A. hydrophila [n = 12]), A. veronii biotype sobria [n = 7], A. caviae [n = 4], A. enchelia [n = 4...

  14. Drug testing in mouse models of tuberculosis and nontuberculous mycobacterial infections.

    PubMed

    Nikonenko, Boris V; Apt, Alexander S

    2013-05-01

    Mice as a species are susceptible to tuberculosis infection while mouse inbred strains present wide spectrum of susceptibility/resistance to this infection. However, non-tuberculosis Mycobacterial infections usually cannot be modeled in mice of common inbred strains. Introduction of specific properties, such as gene mutations, recombinants, targeted gene knockouts significantly extended the use of mice to mimic human Mycobacterial infections, including non-tuberculosis ones. This review describes the available mouse models of tuberculosis and non-tuberculosis infections and drug therapy in these models. Mouse models of non-tuberculosis infections are significantly less developed than tuberculosis models, hampering the development of therapies. PMID:23491715

  15. Efficient reactivation of latent herpes simplex virus from mouse central nervous system tissues.

    PubMed

    Chen, Shih-Heng; Yao, Hui-Wen; Huang, Wen-Yen; Hsu, Kuei-Sen; Lei, Huan-Yao; Shiau, Ai-Li; Chen, Shun-Hua

    2006-12-01

    For decades, numerous ex vivo studies have documented that latent herpes simplex virus (HSV) reactivates efficiently from ganglia, but rarely from the central nervous systems (CNS), of mice when assayed by mincing tissues before explant culture, despite the presence of viral genomes in both sites. Here we show that 88% of mouse brain stems reactivated latent virus when they were dissociated into cell suspensions before ex vivo explant culture. The efficient reactivation of HSV from the mouse CNS was demonstrated with more than one viral strain, viral serotype, and mouse strain, further indicating that the CNS can be an authentic latency site for HSV with the potential to cause recurrent disease. PMID:17005636

  16. Mouse Cleaning Apparatus and Method

    NASA Technical Reports Server (NTRS)

    Williams, Glenn L. (Inventor)

    2005-01-01

    The method of using the mouse pad cleaning apparatus is disclosed and claimed. The method comprises the steps of uncovering the mouse cleaning surface, applying the mouse and ball of the mouse to the cleaning surface, moving the mouse in a rotational pattern on the mouse cleaning surface, removing the mouse form the mouse cleaning surface, washing the cleaning surface, and covering the mouse cleaning surface. A mouse pad cleaning apparatus comprising a plurality of substrates, each said substrate having adhesive thereon, said plurality of substrates residing in and affixed to a receptacle. A single substrate having adhesive, which may be washable or non-washable, thereon may be employed. The washable adhesive may be an organopolysiloxane or gelatinous elastomer.

  17. Mouse or man? Which are pertussis vaccines to protect?

    PubMed

    Preston, N W; Stanbridge, T N

    1976-04-01

    Type 1 strains of Bordetella pertussis can infect mouse brain and have been recovered as type 1 organisms after death. When introduced into the naso-pharynx of the marmoset, they immediately acquired agglutinogen 2 or 3, and the resulting type 1,2 or 1,3 infection persisted for many weeks. As in the child, agglutinogens 2 and/or 3 appear to be essential for infection of the marmoset, whereas they are quite unnecessary in mouse brain. A vaccine (extract or whole cell) containing agglutinogen 1 may be sufficient to pass the mouse protection test but it may fail to immunize children. The mouse test is inadequate even for the screening of such extracts. PMID:177701

  18. Elemental profiles in Emory mouse lens

    SciTech Connect

    Bagchi, M.; Emanuel, K. )

    1991-01-01

    Energy dispersive x-ray microprobe analysis was used to determine the distribution of chloride, potassium, phosphorus and sulfur in the epithelial cells of the lenses obtained from 3 to 7 month old Emory mice and 7 month old cataract resistant strain of Emory mice. Rapidly frozen lenses were fractured in the frozen state and lyophilized. The anterior epithelial cells were analyzed from equator to equator. The results show that the epithelial cells of the 7 month old Emory mouse lens have considerably higher amounts of chloride, sulfur, potassium and phosphorus. Presence of increased amount of potassium in the epithelial cells is intriguing. The data obtained from these experiments show that the changes in the elemental levels of epithelial cells are similar to observed alteration found in the lens fiber mass of 7 month old Emory mouse.

  19. Histomorphological Phenotyping of the Adult Mouse Brain.

    PubMed

    Mikhaleva, Anna; Kannan, Meghna; Wagner, Christel; Yalcin, Binnaz

    2016-01-01

    This article describes a series of standard operating procedures for morphological phenotyping of the mouse brain using basic histology. Many histological studies of the mouse brain use qualitative approaches based on what the human eye can detect. Consequently, some phenotypic information may be missed. Here we describe a quantitative approach for the assessment of brain morphology that is simple and robust. A total of 78 measurements are made throughout the brain at specific and well-defined regions, including the cortex, the hippocampus, and the cerebellum. Experimental design and timeline considerations, including strain background effects, the importance of sectioning quality, measurement variability, and efforts to correct human errors are discussed. © 2016 by John Wiley & Sons, Inc. PMID:27584555

  20. Biological and molecular characterizations of Toxoplasma gondii strains

    USGS Publications Warehouse

    Cole, R.A.; Lindsay, D.S.; Howe, D.K.; Roderick, Constance L.; Dubey, J.P.; Thomas, N.J.; Baeten, L.A.

    2000-01-01

    Toxoplasma gondii was isolated from brain or heart tissue from 15 southern sea otters (Enhydra lutris nereis) in cell cultures. These strains were used to infect mice that developed antibodies to T. gondii as detected in the modified direct agglutination test and had T. gondii tissue cysts in their brains at necropsy. Mouse brains containing tissue cysts from 4 of the strains were fed to 4 cats. Two of the cats excreted T. gondii oocysts in their feces that were infectious for mice. Molecular analyses of 13 strains indicated that they were all type II strains, but that they were genetically distinct from one another.

  1. High temperature strain gage apparent strain compensation

    NASA Technical Reports Server (NTRS)

    Holmes, Harlan K.; Moore, T. C., Sr.

    1992-01-01

    Once an installed strain gage is connected to a strain indicating device and the instrument is balanced, a subsequent change in temperature of the gage installation will generally produce a resistance change in the gage. This purely temperature-induced resistance will be registered by the indicating device as a strain and is referred to as 'apparent strain' to distinguish it from strain due to applied stress. One desirable technique for apparent strain compensation is to employ two identical gages with identical mounting procedures which are connected with a 'half bridge' configuration where gages see the same thermal environment but only one experiences a mechanical strain input. Their connection in adjacent arms of the bridge will then balance the thermally induced apparent strains and, in principle, only the mechanical strain remains. Two approaches that implement this technique are discussed.

  2. Characterization of Virulent West Nile Virus Kunjin Strain, Australia, 2011

    PubMed Central

    Frost, Melinda J.; Zhang, Jing; Edmonds, Judith H.; Prow, Natalie A.; Gu, Xingnian; Davis, Rodney; Hornitzky, Christine; Arzey, Kathleen E.; Finlaison, Deborah; Hick, Paul; Read, Andrew; Hobson-Peters, Jody; May, Fiona J.; Doggett, Stephen L.; Haniotis, John; Russell, Richard C.; Hall, Roy A.; Khromykh, Alexander A.

    2012-01-01

    To determine the cause of an unprecedented outbreak of encephalitis among horses in New South Wales, Australia, in 2011, we performed genomic sequencing of viruses isolated from affected horses and mosquitoes. Results showed that most of the cases were caused by a variant West Nile virus (WNV) strain, WNVNSW2011, that is most closely related to WNV Kunjin (WNVKUN), the indigenous WNV strain in Australia. Studies in mouse models for WNV pathogenesis showed that WNVNSW2011 is substantially more neuroinvasive than the prototype WNVKUN strain. In WNVNSW2011, this apparent increase in virulence over that of the prototype strain correlated with at least 2 known markers of WNV virulence that are not found in WNVKUN. Additional studies are needed to determine the relationship of the WNVNSW2011 strain to currently and previously circulating WNVKUN strains and to confirm the cause of the increased virulence of this emerging WNV strain. PMID:22516173

  3. Biological methods for archiving and maintaining mutant laboratory mice. Part I: conserving mutant strains.

    PubMed

    Fray, Martin D

    2009-01-01

    The mouse is now firmly established as the model organism of choice for scientists studying mammalian biology and human disease. Consequently, a plethora of novel, genetically altered (GA) mouse lines have been created. In addition, the output from the large scale mutagenesis programmes currently under way around the world will increase the collection of GA mouse strains still further. Because of the implications for animal welfare and the constraints on resources, it would be unreasonable to expect anything other than those strains essential for ongoing research programmes to be maintained as breeding colonies. Unfortunately, unless the redundant strains are preserved using robust procedures, which guarantee their recovery, they will be lost to future generations of researchers.This chapter describes some of the preservation methods currently used in laboratories around the world to archive novel mouse strains. PMID:19504080

  4. Geobacteraceae strains and methods

    DOEpatents

    Lovley, Derek R.; Nevin, Kelly P.; Yi, Hana

    2015-07-07

    Embodiments of the present invention provide a method of producing genetically modified strains of electricigenic microbes that are specifically adapted for the production of electrical current in microbial fuel cells, as well as strains produced by such methods and fuel cells using such strains. In preferred embodiments, the present invention provides genetically modified strains of Geobacter sulfurreducens and methods of using such strains.

  5. The ability of airborne Klebsiella pneumoniae to colonize mouse lungs.

    PubMed Central

    Bolister, N. J.; Johnson, H. E.; Wathes, C. M.

    1992-01-01

    A strain of Klebsiella pneumoniae was aerosolized and its survival in air at different relative humidities was studied. Survival was dependent upon relative humidity and aerosols were most stable during storage at a relative humidity of 60%. Mice were exposed to aerosols of K. pneumoniae produced at this humidity and lung samples taken at timed intervals after exposure. Fifteen strains of K. pneumoniae were tested for their ability to colonize mice, but only five were detectable in mouse lungs 7 days after exposure. Three of these strains persisted without an increase in bacterial numbers, regardless of the initial inoculum used. Two strains of K. pneumoniae, designated strains 15 and 16, persisted in a similar manner when used at a low dose; however, when the dose received per lung was increased there was a rapid multiplication of bacteria in the lungs. PMID:1499666

  6. Strains and Sprains

    MedlinePlus

    ... Children's Sports Injuries Computer-Related Repetitive Stress Injuries Knee Injuries Broken Bones, Sprains, and Strains Strains and Sprains ... Pain Going to a Physical Therapist Hamstring Strain Knee Injuries Sports and Exercise Safety Dealing With Sports Injuries ...

  7. Muscle strain (image)

    MedlinePlus

    A muscle strain is the stretching or tearing of muscle fibers. A muscle strain can be caused by sports, exercise, a ... something that is too heavy. Symptoms of a muscle strain include pain, tightness, swelling, tenderness, and the ...

  8. Muscle strain treatment

    MedlinePlus

    Treatment - muscle strain ... Question: How do you treat a muscle strain ? Answer: Rest the strained muscle and apply ice for the first few days after the injury. Anti-inflammatory medicines or acetaminophen ( ...

  9. The mouse dead-end gene isoform alpha is necessary for germ cell and embryonic viability.

    PubMed

    Bhattacharya, Chitralekha; Aggarwal, Sita; Zhu, Rui; Kumar, Madhu; Zhao, Ming; Meistrich, Marvin L; Matin, Angabin

    2007-03-30

    Inactivation of the dead-end (Dnd1) gene in the Ter mouse strain results in depletion of primordial germ cells (PGCs) so that mice become sterile. However, on the 129 mouse strain background, loss of Dnd1 also increases testicular germ cell tumor incidence in parallel to PGC depletion. We report that inactivation of Dnd1 also affects embryonic viability in the 129 strain. Mouse Dnd1 encodes two protein isoforms, DND1-isoform alpha (DND1-alpha) and DND1-isoform beta (DND1-beta). Using isoform-specific antibodies, we determined DND1-alpha is expressed in embryos and embryonic gonads whereas DND1-beta expression is restricted to germ cells of the adult testis. Our data implicate DND1-alpha isoform to be necessary for germ cell viability and therefore its loss in Ter mice results in PGC depletion, germ cell tumor development and partial embryonic lethality in the 129 strain. PMID:17291453

  10. Recent Progress in Magnetic Resonance Imaging of the Embryonic and Neonatal Mouse Brain

    PubMed Central

    Wu, Dan; Zhang, Jiangyang

    2016-01-01

    The laboratory mouse has been widely used as a model system to investigate the genetic control mechanisms of mammalian brain development. Magnetic resonance imaging (MRI) is an important tool to characterize changes in brain anatomy in mutant mouse strains and injury progression in mouse models of fetal and neonatal brain injury. Progress in the last decade has enabled us to acquire MRI data with increasing anatomical details from the embryonic and neonatal mouse brain. High-resolution ex vivo MRI, especially with advanced diffusion MRI methods, can visualize complex microstructural organizations in the developing mouse brain. In vivo MRI of the embryonic mouse brain, which is critical for tracking anatomical changes longitudinally, has become available. Applications of these techniques may lead to further insights into the complex and dynamic processes of brain development. PMID:26973471

  11. Periodic properties of the histaminergic system of the mouse brain.

    PubMed

    Rozov, Stanislav V; Zant, Janneke C; Karlstedt, Kaj; Porkka-Heiskanen, Tarja; Panula, Pertti

    2014-01-01

    Brain histamine is involved in the regulation of the sleep-wake cycle and alertness. Despite the widespread use of the mouse as an experimental model, the periodic properties of major markers of the mouse histaminergic system have not been comprehensively characterized. We analysed the daily levels of histamine and its first metabolite, 1-methylhistamine, in different brain structures of C57BL/6J and CBA/J mouse strains, and the mRNA level and activity of histidine decarboxylase and histamine-N-methyltransferase in C57BL/6J mice. In the C57BL/6J strain, histamine release, assessed by in vivo microdialysis, underwent prominent periodic changes. The main period was 24 h peaking during the activity period. Additional 8 h periods were also observed. The release was highly positively correlated with active wakefulness, as shown by electroencephalography. In both mouse strains, tissue histamine levels remained steady for 24 h in all structures except for the hypothalamus of CBA/J mice, where 24-h periodicity was observed. Brain tissue 1-methylhistamine levels in both strains reached their maxima in the periods of activity. The mRNA level of histidine decarboxylase in the tuberomamillary nucleus and the activities of histidine decarboxylase and histamine-N-methyltransferase in the striatum and cortex did not show a 24-h rhythm, whereas in the hypothalamus the activities of both enzymes had a 12-h periodicity. These results show that the activities of histamine-metabolizing enzymes are not under simple direct circadian regulation. The complex and non-uniform temporal patterns of the histaminergic system of the mouse brain suggest that histamine is strongly involved in the maintenance of active wakefulness. PMID:24438489

  12. Positional cloning of the mouse saccharin preference (Sac) locus

    PubMed Central

    Bachmanov, Alexander A.; Li, Xia; Reed, Danielle R.; Ohmen, Jeffery D.; Li, Shanru; Chen, Zhenyu; Tordoff, Michael G.; de Jong, Pieter J.; Wu, Chenyan; West, David B.; Chatterjee, Alu; Ross, David A.; Beauchamp, Gary K.

    2013-01-01

    Differences in sweetener intake among inbred strains of mice are partially determined by allelic variation of the saccharin preference (Sac) locus. Genetic and physical mapping limited a critical genomic interval containing Sac to a 194-kb DNA fragment. Sequencing and annotation of this region identified a gene (Tas1r3) encoding the third member of the T1R family of putative taste receptors, T1R3. Introgression by serial backcrossing of the 194-kb chromosomal fragment containing the Tas1r3 allele from the high-sweetener preferring C57BL/6ByJ strain onto the genetic background of the low-sweetener preferring 129P3/J strain rescued its low sweetener preference phenotype. Polymorphisms of Tas1r3 that are likely to have functional significance were identified using analysis of genomic sequences and sweetener preference phenotypes of genealogically distant mouse strains. Tas1r3 has two common haplotypes, consisting of six single nucleotide polymorphisms: one haplotype was found in mouse strains with elevated sweetener preference and the other in strains relatively indifferent to sweeteners. This study provides compelling evidence that Tas1r3 is equivalent to the Sac locus and that the T1R3 receptor responds to sweeteners. PMID:11555487

  13. Human-mouse interspecies collagen I heterotrimer is functional during embryonic development of Mov13 mutant mouse embryos.

    PubMed Central

    Wu, H; Bateman, J F; Schnieke, A; Sharpe, A; Barker, D; Mascara, T; Eyre, D; Bruns, R; Krimpenfort, P; Berns, A

    1990-01-01

    To investigate whether the human pro alpha 1(I) collagen chain could form an in vivo functional interspecies heterotrimer with the mouse pro alpha 2(I) collagen chain, we introduced the human COL1A1 gene into Mov13 mice which have a functional deletion of the endogenous COL1A1 gene. Transgenic mouse strains (HucI and HucII) carrying the human COL1A1 gene were first generated by microinjecting the COL1A1 gene into wild-type mouse embryos. Genetic evidence indicated that the transgene in the HucI strain was closely linked to the endogenous mouse COL1A1 gene and was X linked in the HucII transgenic strain. Northern (RNA) blot and S1 protection analyses showed that the transgene was expressed in the appropriate tissue-specific manner and as efficiently as the endogenous COL1A1 gene. HucII mice were crossed with Mov13 mice to transfer the human transgene into the mutant strain. Whereas homozygous Mov13 embryos die between days 13 and 14 of gestation, the presence of the transgene permitted apparently normal development of the mutant embryos to birth. This indicated that the mouse-human interspecies collagen I heterotrimer was functional in the animal. The rescue was, however, only partial, as all homozygotes died within 36 h after delivery, with signs of internal bleeding. This could have been due to a functional defect in the interspecies hybrid collagen. Extensive analysis failed to reveal any biochemical or morphological abnormalities of the collagen I molecules in Mov13-HucII embryos.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:1690840

  14. Mouse models for neural tube closure defects.

    PubMed

    Juriloff, D M; Harris, M J

    2000-04-12

    Neural tube closure defects (NTDs), in particular anencephaly and spina bifida, are common human birth defects (1 in 1000), their genetics is complex and their risk is reduced by periconceptional maternal folic acid supplementation. There are > 60 mouse mutants and strains with NTDs, many reported within the past 2 years. Not only are NTD mutations at loci widely heterogeneous in function, but also most of the mutants demonstrate variable low penetrance and some show complex inheritance patterns (e.g. SELH/Bc, Abl / Arg, Mena / Profilin1 ). In most of these mouse models, the NTDs are exencephaly (equivalent to anencephaly) or spina bifida or both, reflecting failure of neural fold elevation in well defined, mechanistically distinct elevation zones. NTD risk is reduced in various models by different maternal nutrient supplements, including folic acid ( Pax3, Cart1, Cd mutants), inositol ( ct ) and methionine ( Axd ). Lack of de novo methylation in embryos ( Dnmt3b -null) leads to NTD risk, and we suggest a potential link between methylation and the observed female excess among cranial NTDs in several models. Some surprising NTD mutants ( Gadd45a, Terc, Trp53 ) suggest that genes with a basic mitotic function also have a function specific to neural fold elevation. The genes mutated in several mouse NTD models involve actin regulation ( Abl/Arg, Macs, Mena/Profilin1, Mlp, Shrm, Vcl ), support the postulated key role of actin in neural fold elevation, and may be a good candidate pathway to search for human NTD genes. PMID:10767323

  15. Orthotopic Hind Limb Transplantation in the Mouse.

    PubMed

    Furtmüller, Georg J; Oh, Byoungchol; Grahammer, Johanna; Lin, Cheng-Hung; Sucher, Robert; Fryer, Madeline L; Raimondi, Giorgio; Lee, W P Andrew; Brandacher, Gerald

    2016-01-01

    In vivo animal model systems, and in particular mouse models, have evolved into powerful and versatile scientific tools indispensable to basic and translational research in the field of transplantation medicine. A vast array of reagents is available exclusively in this setting, including mono- and polyclonal antibodies for both diagnostic and interventional applications. In addition, a vast number of genotyped, inbred, transgenic, and knock out strains allow detailed investigation of the individual contributions of humoral and cellular components to the complex interplay of an immune response and make the mouse the gold standard for immunological research. Vascularized Composite Allotransplantation (VCA) delineates a novel field of transplantation using allografts to replace "like with like" in patients suffering traumatic or congenital tissue loss. This surgical methodological protocol shows the use of a non-suture cuff technique for super-microvascular anastomosis in an orthotopic mouse hind limb transplantation model. The model specifically allows for comparison between established paradigms in solid organ transplantation with a novel form of transplants consisting of various different tissue components. Uniquely, this model allows for the transplantation of a viable vascularized bone marrow compartment and niche that have the potential to exert a beneficial effect on the balance of immune acceptance and rejection. This technique provides a tool to investigate alloantigen recognition and allograft rejection and acceptance, as well as enables the pursuit of functional nerve regeneration studies to further advance this novel field of transplantation. PMID:26967527

  16. Colonization, mouse-style

    PubMed Central

    2010-01-01

    Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325 PMID:20977781

  17. MOUSE UNCERTAINTY ANALYSIS SYSTEM

    EPA Science Inventory

    The original MOUSE (Modular Oriented Uncertainty System) system was designed to deal with the problem of uncertainties in Environmental engineering calculations, such as a set of engineering cost or risk analysis equations. t was especially intended for use by individuals with li...

  18. Mouse Model of Coxiella burnetii Aerosolization.

    PubMed

    Melenotte, Cléa; Lepidi, Hubert; Nappez, Claude; Bechah, Yassina; Audoly, Gilles; Terras, Jérôme; Raoult, Didier; Brégeon, Fabienne

    2016-07-01

    Coxiella burnetii is mainly transmitted by aerosols and is responsible for multiple-organ lesions. Animal models have shown C. burnetii pathogenicity, but long-term outcomes still need to be clarified. We used a whole-body aerosol inhalation exposure system to mimic the natural route of infection in immunocompetent (BALB/c) and severe combined immunodeficient (SCID) mice. After an initial lung inoculum of 10(4) C. burnetii cells/lung, the outcome, serological response, hematological disorders, and deep organ lesions were described up to 3 months postinfection. C. burnetii-specific PCR, anti-C. burnetii immunohistochemistry, and fluorescent in situ hybridization (FISH) targeting C. burnetii-specific 16S rRNA completed the detection of the bacterium in the tissues. In BALB/c mice, a thrombocytopenia and lymphopenia were first observed, prior to evidence of C. burnetii replication. In all SCID mouse organs, DNA copies increased to higher levels over time than in BALB/c ones. Clinical signs of discomfort appeared in SCID mice, so follow-up had to be shortened to 2 months in this group. At this stage, all animals presented bone, cervical, and heart lesions. The presence of C. burnetii could be attested in situ for all organs sampled using immunohistochemistry and FISH. This mouse model described C. burnetii Nine Mile strain spread using aerosolization in a way that corroborates the pathogenicity of Q fever described in humans and completes previously published data in mouse models. C. burnetii infection occurring after aerosolization in mice thus seems to be a useful tool to compare the pathogenicity of different strains of C. burnetii. PMID:27160294

  19. Program Calibrates Strain Gauges

    NASA Technical Reports Server (NTRS)

    Okazaki, Gary D.

    1991-01-01

    Program dramatically reduces personnel and time requirements for acceptance tests of hardware. Data-acquisition system reads output from Wheatstone full-bridge strain-gauge circuit and calculates strain by use of shunt calibration technique. Program nearly instantaneously tabulates and plots strain data against load-cell outputs. Modified to acquire strain data for other specimens wherever full-bridge strain-gauge circuits used. Written in HP BASIC.

  20. Superlattice strain gage

    DOEpatents

    Noel, Bruce W.; Smith, Darryl L.; Sinha, Dipen N.

    1990-01-01

    A strain gage comprising a strained-layer superlattice crystal exhibiting piezoelectric properties is described. A substrate upon which such a strained-layer superlattice crystal has been deposited is attached to an element to be monitored for strain. A light source is focused on the superlattice crystal and the light reflected from, passed through, or emitted from the crystal is gathered and compared with previously obtained optical property data to determine the strain in the element.

  1. Superlattice strain gage

    DOEpatents

    Noel, B.W.; Smith, D.L.; Sinha, D.N.

    1988-06-28

    A strain gage comprising a strained-layer superlattice crystal exhibiting piezoelectric properties is described. A substrate upon which such a strained-layer superlattice crystal has been deposited is attached to an element to be monitored for strain. A light source is focused on the superlattice crystal and the light reflected from, passed through, or emitted from the crystal is gathered and compared with previously obtained optical property data to determine the strain in the element. 8 figs.

  2. Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism.

    PubMed

    Ellegood, Jacob; Crawley, Jacqueline N

    2015-07-01

    In order to understand the consequences of the mutation on behavioral and biological phenotypes relevant to autism, mutations in many of the risk genes for autism spectrum disorder have been experimentally generated in mice. Here, we summarize behavioral outcomes and neuroanatomical abnormalities, with a focus on high-resolution magnetic resonance imaging of postmortem mouse brains. Results are described from multiple mouse models of autism spectrum disorder and comorbid syndromes, including the 15q11-13, 16p11.2, 22q11.2, Cntnap2, Engrailed2, Fragile X, Integrinβ3, MET, Neurexin1a, Neuroligin3, Reelin, Rett, Shank3, Slc6a4, tuberous sclerosis, and Williams syndrome models, and inbred strains with strong autism-relevant behavioral phenotypes, including BTBR and BALB. Concomitant behavioral and neuroanatomical abnormalities can strengthen the interpretation of results from a mouse model, and may elevate the usefulness of the model system for therapeutic discovery. PMID:26036957

  3. The Mouse That Soared

    NASA Astrophysics Data System (ADS)

    2004-09-01

    Astronomers have used an X-ray image to make the first detailed study of the behavior of high-energy particles around a fast moving pulsar. The image, from NASA's Chandra X-ray Observatory, shows the shock wave created as a pulsar plows supersonically through interstellar space. These results will provide insight into theories for the production of powerful winds of matter and antimatter by pulsars. Chandra's image of the glowing cloud, known as the Mouse, shows a stubby bright column of high-energy particles, about four light years in length, swept back by the pulsar's interaction with interstellar gas. The intense source at the head of the X-ray column is the pulsar, estimated to be moving through space at about 1.3 million miles per hour. VLA Radio Image of the Mouse, Full Field VLA Radio Image of the Mouse, Full Field A cone-shaped cloud of radio-wave-emitting particles envelopes the X-ray column. The Mouse, a.k.a. G359.23-0.82, was discovered in 1987 by radio astronomers using the National Science Foundation's Very Large Array in New Mexico. It gets its name from its appearance in radio images that show a compact snout, a bulbous body, and a remarkable long, narrow, tail that extends for about 55 light years. "A few dozen pulsar wind nebulae are known, including the spectacular Crab Nebula, but none have the Mouse's combination of relatively young age and incredibly rapid motion through interstellar space," said Bryan Gaensler of the Harvard-Smithsonian Center for Astrophysics and lead author of a paper on the Mouse that will appear in an upcoming issue of The Astrophysical Journal. "We effectively are seeing a supersonic cosmic wind tunnel, in which we can study the effects of a pulsar's motion on its pulsar wind nebula, and test current theories." Illustration of the Mouse System Illustration of the Mouse System Pulsars are known to be rapidly spinning, highly magnetized neutron stars -- objects so dense that a mass equal to that of the Sun is packed into a

  4. Mouse Phenome Database

    PubMed Central

    Grubb, Stephen C.; Bult, Carol J.; Bogue, Molly A.

    2014-01-01

    The Mouse Phenome Database (MPD; phenome.jax.org) was launched in 2001 as the data coordination center for the international Mouse Phenome Project. MPD integrates quantitative phenotype, gene expression and genotype data into a common annotated framework to facilitate query and analysis. MPD contains >3500 phenotype measurements or traits relevant to human health, including cancer, aging, cardiovascular disorders, obesity, infectious disease susceptibility, blood disorders, neurosensory disorders, drug addiction and toxicity. Since our 2012 NAR report, we have added >70 new data sets, including data from Collaborative Cross lines and Diversity Outbred mice. During this time we have completely revamped our homepage, improved search and navigational aspects of the MPD application, developed several web-enabled data analysis and visualization tools, annotated phenotype data to public ontologies, developed an ontology browser and released new single nucleotide polymorphism query functionality with much higher density coverage than before. Here, we summarize recent data acquisitions and describe our latest improvements. PMID:24243846

  5. Mouse phenome database.

    PubMed

    Grubb, Stephen C; Bult, Carol J; Bogue, Molly A

    2014-01-01

    The Mouse Phenome Database (MPD; phenome.jax.org) was launched in 2001 as the data coordination center for the international Mouse Phenome Project. MPD integrates quantitative phenotype, gene expression and genotype data into a common annotated framework to facilitate query and analysis. MPD contains >3500 phenotype measurements or traits relevant to human health, including cancer, aging, cardiovascular disorders, obesity, infectious disease susceptibility, blood disorders, neurosensory disorders, drug addiction and toxicity. Since our 2012 NAR report, we have added >70 new data sets, including data from Collaborative Cross lines and Diversity Outbred mice. During this time we have completely revamped our homepage, improved search and navigational aspects of the MPD application, developed several web-enabled data analysis and visualization tools, annotated phenotype data to public ontologies, developed an ontology browser and released new single nucleotide polymorphism query functionality with much higher density coverage than before. Here, we summarize recent data acquisitions and describe our latest improvements. PMID:24243846

  6. Miniature biaxial strain transducer

    NASA Technical Reports Server (NTRS)

    Hoffman, I. S. (Inventor)

    1976-01-01

    A reusable miniature strain transducer for use in the measurement of static or quasi-static, high level, biaxial strain on the surface of test specimens or structures was studied. Two cantilever arms, constructed by machining the material to appropriate flexibility, are self-aligning and constitute the transducing elements of the device. Used in conjunction with strain gages, the device enables testing beyond normal gage limits for high strains and number of load cycles. The device does not require conversion computations since the electrical output of the strain gages is directly proportional to the strain measured.

  7. ISOLATION OF MOUSE NEUTROPHILS

    PubMed Central

    Swamydas, Muthulekha; Luo, Yi; Dorf, Martin E.; Lionakis, Michail S.

    2015-01-01

    Neutrophils represent the first line of defense against bacterial and fungal pathogens. Indeed, patients with inherited and acquired qualitative and quantitative neutrophil defects are at high risk for developing bacterial and fungal infections and suffering adverse outcomes from these infections. Therefore, research aiming at defining the molecular factors that modulate neutrophil effector function under homeostatic conditions and during infection is essential for devising strategies to augment neutrophil function and improve the outcome of infected individuals. This unit describes a reproducible density gradient centrifugation-based protocol that can be applied in any laboratory to harvest large numbers of highly enriched and highly viable neutrophils from the bone marrow of mice both at the steady state and following infection with Candida albicans as described in UNIT 19.6. In another protocol, we also present a method that combines gentle enzymatic tissue digestion with a positive immunomagnetic selection technique or Fluorescence-activated cell sorting (FACS) to harvest highly pure and highly viable preparations of neutrophils directly from mouse tissues such as the kidney, the liver or the spleen. Finally, methods for isolating neutrophils from mouse peritoneal fluid and peripheral blood are included. Mouse neutrophils isolated by these protocols can be used for examining several aspects of cellular function ex vivo including pathogen binding, phagocytosis and killing, neutrophil chemotaxis, oxidative burst, degranulation and cytokine production, and for performing neutrophil adoptive transfer experiments. PMID:26237011

  8. Phenotypic and functional characterization of Bst+/− mouse retina

    PubMed Central

    Riazifar, Hamidreza; Sun, Guoli; Wang, Xinjian; Rupp, Alan; Vemaraju, Shruti; Ross-Cisneros, Fred N.; Lang, Richard A.; Sadun, Alfredo A.; Hattar, Samer; Guan, Min-Xin; Huang, Taosheng

    2015-01-01

    ABSTRACT The belly spot and tail (Bst+/−) mouse phenotype is caused by mutations of the ribosomal protein L24 (Rpl24). Among various phenotypes in Bst+/− mice, the most interesting are its retinal abnormalities, consisting of delayed closure of choroid fissures, decreased ganglion cells and subretinal vascularization. We further characterized the Bst+/− mouse and investigated the underlying molecular mechanisms to assess the feasibility of using this strain as a model for stem cell therapy of retinal degenerative diseases due to retinal ganglion cell (RGC) loss. We found that, although RGCs are significantly reduced in retinal ganglion cell layer in Bst+/− mouse, melanopsin+ RGCs, also called ipRGCs, appear to be unchanged. Pupillary light reflex was completely absent in Bst+/− mice but they had a normal circadian rhythm. In order to examine the pathological abnormalities in Bst+/− mice, we performed electron microscopy in RGC and found that mitochondria morphology was deformed, having irregular borders and lacking cristae. The complex activities of the mitochondrial electron transport chain were significantly decreased. Finally, for subretinal vascularization, we also found that angiogenesis is delayed in Bst+/− associated with delayed hyaloid regression. Characterization of Bst+/− retina suggests that the Bst+/− mouse strain could be a useful murine model. It might be used to explore further the pathogenesis and strategy of treatment of retinal degenerative diseases by employing stem cell technology. PMID:26035379

  9. A Comparison of Some Organizational Characteristics of the Mouse Central Retina and the Human Macula

    PubMed Central

    Hoo, Juyea; Yee, Claudine; Williams, David S.

    2015-01-01

    Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch’s membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch’s membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident. PMID:25923208

  10. Strains and Sprains

    MedlinePlus

    ... move the injured part, and you might even think you have broken a bone. How Does a Strain or Sprain Happen? Strains often happen when you put a lot of pressure on a muscle or you push it too far, such as when lifting a heavy object. Strains may be more likely to happen if ...

  11. Sprains and Strains

    MedlinePlus

    ... happens. A strain is a stretched or torn muscle or tendon. Tendons are tissues that connect muscle to bone. Twisting or pulling these tissues can ... suddenly or develop over time. Back and hamstring muscle strains are common. Many people get strains playing ...

  12. In Vivo Axial Loading of the Mouse Tibia

    PubMed Central

    Melville, Katherine M.; Robling, Alexander G.

    2015-01-01

    Summary Non-invasive methods to apply controlled, cyclic loads to the living skeleton are used as an anabolic agent to stimulate new bone formation in adults and enhance bone mass accrual in growing animals. These methods are also invaluable for understanding bone signaling pathways. Our focus here is on a particular loading model: in vivo axial compression of the mouse tibia. An advantage of loading the tibia is that changes are present in both the cancellous envelope of the proximal tibia and the cortical bone of the tibial diaphysis. To load the tibia of the mouse axially in vivo, a cyclic compressive load is applied up to five times a week to a single tibia per mouse for a duration lasting from 1 day to 6 weeks. With the contralateral limb as an internal control, the anabolic response of the skeleton to mechanical stimuli can be studied in a pairwise experimental design. Here, we describe the key parameters that must be considered before beginning an in vivo mouse tibial loading experiment, including methods for in vivo strain gauging of the tibial midshaft, and then we describe general methods for loading the mouse tibia for an experiment lasting multiple days. PMID:25331046

  13. Regulation of cytochrome P-450 monooxygenases in the mouse

    SciTech Connect

    Kelley, M.F.

    1986-01-01

    Recently, the compound 1,4-bis(2-(3,4-dichloropyridyloxy)) benzene (TCPOBOP) has been identified as a highly potent phenobabital-like agonist in mice. This finding has led to the suggestion that a receptor-mediated process may govern the induction of cytochrome P-450 monooxygenases by phenobarbital and phenobarbital-like agonists. This dissertation examines: (1) the effects of structural alterations of the TCPOBOP molecule on enzyme induction activity, (2) the induction response to phenobarbital and TCPOBOP among inbred mouse strains, (3) the spectrum of monooxygenase activities induced by phenobarbital and TCPOBOP compared to 3-methylcholanthrene, isosafrole and pregnenolone 16..cap alpha..-carbonitrile (PCN) and (4) the binding of (/sup 3/H) TCPOBOP in hepatic cytosol. Changes in the structure of the pyridyloxy or benzene rings markedly affect enzyme induction activity and provide additional indirect evidence for a receptor-mediated response. An evaluation of monooxygenase induction by TCPOBOP for 27 inbred mouse strains and by phenobarbital for 15 inbred mouse strains failed to identify a strain which was completely nonresponsive to these compounds, although several strains exhibited decreased responsiveness for select monooxygenase reactions. TCPOBOP, PCN and phenobarbital were all found to significantly increase the rate of hydroxylation of testosterone at the 2..cap alpha..-, 6..beta..- and 15..beta..- positions but only TCPOBOP and phenobarbital dramatically increased the rate of pentoxyresorufin O-dealkylation. The results demonstrates that TCPOBOP most closely resembles phenobarbital in its mode of monooxygenase induction in mice. Sucrose density gradient analysis of (/sup 3/H) TCPOBOP-hepatic cytosol incubations failed to identify specific, saturable binding of (/sup 3/H) TCPOBOP to cytosolic marcomolecular elements.

  14. The Mouse Olfactory Peduncle

    PubMed Central

    Brunjes, Peter C; Kay, Rachel B; Arrivillaga, J. P

    2012-01-01

    The olfactory peduncle, the region connecting the olfactory bulb with the basal forebrain, contains several neural areas that have received relatively little attention. The present work includes studies that provide an overview of the region in the mouse. An analysis of cell soma size in pars principalis (pP) of the anterior olfactory nucleus (AON) revealed considerable differences in tissue organization between mice and rats. An unbiased stereological study of neuron number in the cell-dense regions of pars externa (pE) and pP of the AON of 3, 12 and 24 month-old mice indicated that pE has about 16,500 cells in 0.043 mm3and pP about 58,300 cells in 0.307 mm3. Quantitative Golgi studies of pyramidal neurons in pP suggested that mouse neurons are similar though smaller to those of the rat. An immunohistochemical analysis demonstrated that all peduncular regions (pE, pP, the dorsal peduncular cortex, ventral tenia tecta, and anterior olfactory tubercle and piriform cortex) have cells that express either calbindin, calretinin, parvalbumin, somatostatin, vasoactive intestinal polypeptide, neuropeptide Y or cholecystokinin (antigens commonly co-expressed by subspecies of GABAergic neurons), though the relative numbers of each cell type differs between zones. Finally, an electron microscopic comparison of the organization of myelinated fibers in lateral olfactory tract in the anterior and posterior peduncle indicated that the region is less orderly in mice than in the rat. The results provide a caveat for investigators who generalize data between species as both similarities and differences between the laboratory mouse and rat were observed. PMID:21618219

  15. Virulence factors in Escherichia coli strains isolated from Swedish piglets with diarrhea.

    PubMed Central

    Söderlind, O; Thafvelin, B; Möllby, R

    1988-01-01

    Parenteral vaccination of sows against Escherichia coli diarrhea in their newborn piglets has become more common during the last decade in Sweden, and the vaccination has generally had positive effects. For more than 20 years we have investigated E. coli strains isolated from piglets and weaned pigs with enteric disorders, noting the presence of O groups, enterotoxins, and adhesins. There has been a continuous change in the frequency of these virulence factors. The present study was performed during 1983 and 1984 to follow this change, since such information is essential for the proper choice of vaccines. A total of 856 E. coli strains were obtained from 683 herds divided into three age groups: 1 to 6 days old, 1 to 6 weeks old, and weaned pigs. O group 149 still dominated in the last two age groups, while O group 101 was, for the first time, the most frequent O group in neonatal piglets. All but four O149 strains carried the K88 antigen, which was found in only one other strain (O group 8). K99 antigen was most often found in O groups 101 and 64, and among all the K99 strains ST mouse was the most common (44 of 57), followed by ST mouse-ST pig strains (12 of 57). The 987P antigen was demonstrated in 26 strains belonging to O groups 141 and OX46 and nontypable strains. Two strains belonging to O group 101 were positive for F41 antigen; one of them also carried the K99 antigen. Among all non-O149 strains, ST mouse was the most common type of enterotoxigenic E. coli ( n = 88), followed in decreasing order by ST mouse-ST pig strains ( n = 69) and ST pig strains ( n = 33). In 114 strains producing enterotoxins no adhesive factor was found. Thus, vaccination of the Swedish sow population for more than 5 years with vaccines containing O149 and K88 antigens has apparently changed the pattern of enterotoxigenic E. coli in neonatal diarrhea. The frequency of O149:K88 strains has been reduced, and O101:K99:ST mouse strains now dominate. However, O149 strains remain the

  16. A Transgenic Mouse Model of Poliomyelitis.

    PubMed

    Koike, Satoshi; Nagata, Noriyo

    2016-01-01

    Transgenic mice (tg mice) that express the human poliovirus receptor (PVR), CD155, are susceptible to poliovirus and develop a neurological disease that resembles human poliomyelitis. Assessment of the neurovirulence levels of poliovirus strains, including mutant viruses produced by reverse genetics, circulating vaccine-derived poliovirus, and vaccine candidates, is useful for basic research of poliovirus pathogenicity, the surveillance of circulating polioviruses, and the quality control of oral live poliovirus vaccines, and does not require the use of monkeys. Furthermore, PVR-tg mice are useful for studying poliovirus tissue tropism and host immune responses. PVR-tg mice can be bred with mice deficient in the genes involved in viral pathogenicity. This report describes the methods used to analyze the pathogenicity and immune responses of poliovirus using the PVR-tg mouse model. PMID:26983733

  17. Chandra Catches the `Mouse'

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Astronomers have used an x-ray image to make the first detailed study of the behavior of high-energy particles around a fast moving pulsar. This image, from NASA's Chandra X-Ray Observatory (CXO), shows the shock wave created as a pulsar plows supersonically through interstellar space. These results will provide insight into theories for the production of powerful winds of matter and antimatter by pulsars. Chandra's image of the glowing cloud, known as the Mouse, shows a stubby bright column of high-energy particles, about four light years in length, swept back by the pulsar's interaction with interstellar gas. The intense source at the head of the X-ray column is the pulsar, estimated to be moving through space at about 1.3 million miles per hour. A cone-shaped cloud of radio-wave-emitting particles envelopes the x-ray column. The Mouse, a.k.a. G359.23-0.82, was discovered in 1987 by radio astronomers using the National Science Foundation's Very Large Array in New Mexico. G359.23-0.82 gets its name from its appearance in radio images that show a compact snout, a bulbous body, and a remarkable long, narrow, tail that extends for about 55 light years. NASA's Marshall Space Flight Center in Huntsville, Alabama manages the Chandler program.

  18. KRAS Mouse Models

    PubMed Central

    O’Hagan, Rónán C.; Heyer, Joerg

    2011-01-01

    KRAS is a potent oncogene and is mutated in about 30% of all human cancers. However, the biological context of KRAS-dependent oncogenesis is poorly understood. Genetically engineered mouse models of cancer provide invaluable tools to study the oncogenic process, and insights from KRAS-driven models have significantly increased our understanding of the genetic, cellular, and tissue contexts in which KRAS is competent for oncogenesis. Moreover, variation among tumors arising in mouse models can provide insight into the mechanisms underlying response or resistance to therapy in KRAS-dependent cancers. Hence, it is essential that models of KRAS-driven cancers accurately reflect the genetics of human tumors and recapitulate the complex tumor-stromal intercommunication that is manifest in human cancers. Here, we highlight the progress made in modeling KRAS-dependent cancers and the impact that these models have had on our understanding of cancer biology. In particular, the development of models that recapitulate the complex biology of human cancers enables translational insights into mechanisms of therapeutic intervention in KRAS-dependent cancers. PMID:21779503

  19. [Genetics of mouse-hole].

    PubMed

    Jordan, Bertrand

    2013-04-01

    The Oldfield mouse and the Deer mouse build very different burrows in nature and also in the laboratory. This behaviour is innate and, in a series of beautiful experiments making use of new generation sequencing for genetic mapping, the authors map the burrow architecture to a very small number of loci and demonstrate modular evolution of behaviour. PMID:23621941

  20. Utilising the resources of the International Knockout Mouse Consortium: the Australian experience.

    PubMed

    Cotton, Leanne M; Meilak, Michelle L; Templeton, Tanya; Gonzales, Jose G; Nenci, Arianna; Cooney, Melissa; Truman, Dirk; Rodda, Fleur; Lynas, Alyce; Viney, Elizabeth; Rosenthal, Nadia; Bianco, Deborah M; O'Bryan, Moira K; Smyth, Ian M

    2015-04-01

    Mouse models play a key role in the understanding gene function, human development and disease. In 2007, the Australian Government provided funding to establish the Monash University embryonic stem cell-to-mouse (ES2M) facility. This was part of the broader Australian Phenomics Network, a national infrastructure initiative aimed at maximising access to global resources for understanding gene function in the mouse. The remit of the ES2M facility is to provide subsidised access for Australian biomedical researchers to the ES cell resources available from the International Knockout Mouse Consortium (IKMC). The stated aim of the IKMC is to generate a genetically modified mouse ES cell line for all of the ~23,000 genes in the mouse genome. The principal function of the Monash University ES2M service is to import genetically modified ES cells into Australia and to convert them into live mice with the potential to study human disease. Through advantages of economy of scale and established relationships with ES cell repositories worldwide, we have created over 110 germline mouse strains sourced from all of the major ES providers worldwide. We comment on our experience in generating these mouse lines; providing a snapshot of a "clients" perspective of using the IKMC resource and one which we hope will serve as a guide to other institutions or organisations contemplating establishing a similar centralised service. PMID:25645994

  1. Elevated temperature strain gages

    NASA Technical Reports Server (NTRS)

    Brittain, J. O.; Geslin, D.; Lei, J. F.

    1986-01-01

    One of the goals of the HOST Program is the development of electrical resistance strain gages for static strain measurements at temperatures equal to or greater than 1273 K. Strain gage materials must have a reproducible or predictable response to temperature, time and strain. It is the objective of this research to investigate criteria for the selection of materials for such applications through electrical properties studies. The results of the investigation of two groups of materials, refractory compounds and binary alloy solid solutions are presented.

  2. Thin film strain transducer

    NASA Technical Reports Server (NTRS)

    Rand, J. L. (Inventor)

    1984-01-01

    A strain transducer system and process for making the same is disclosed. A beryllium copper ring having four strain gages is electrically connected in Wheatstone bridge fashion to the output instrumentation. Tabs are bonded to a balloon or like surface with strain on the surface causing bending of a ring which provides an electrical signal through the gages proportional to the surface strain. A photographic pattern of a one half ring segment as placed on a sheet of beryllium copper for chem-mill etch formation is illustrated.

  3. Can strain magnetize light?

    NASA Astrophysics Data System (ADS)

    2013-02-01

    Strain in photonic structures can induce pseudomagnetic fields and Landau levels. Nature Photonics spoke to Mordechai Segev, Mikael Rechtsman, Alexander Szameit and Julia Zeuner about their unique approach.

  4. Whole mouse cryo-imaging

    NASA Astrophysics Data System (ADS)

    Wilson, David; Roy, Debashish; Steyer, Grant; Gargesha, Madhusudhana; Stone, Meredith; McKinley, Eliot

    2008-03-01

    The Case cryo-imaging system is a section and image system which allows one to acquire micron-scale, information rich, whole mouse color bright field and molecular fluorescence images of an entire mouse. Cryo-imaging is used in a variety of applications, including mouse and embryo anatomical phenotyping, drug delivery, imaging agents, metastastic cancer, stem cells, and very high resolution vascular imaging, among many. Cryo-imaging fills the gap between whole animal in vivo imaging and histology, allowing one to image a mouse along the continuum from the mouse -> organ -> tissue structure -> cell -> sub-cellular domains. In this overview, we describe the technology and a variety of exciting applications. Enhancements to the system now enable tiled acquisition of high resolution images to cover an entire mouse. High resolution fluorescence imaging, aided by a novel subtraction processing algorithm to remove sub-surface fluorescence, makes it possible to detect fluorescently-labeled single cells. Multi-modality experiments in Magnetic Resonance Imaging and Cryo-imaging of a whole mouse demonstrate superior resolution of cryo-images and efficiency of registration techniques. The 3D results demonstrate the novel true-color volume visualization tools we have developed and the inherent advantage of cryo-imaging in providing unlimited depth of field and spatial resolution. The recent results continue to demonstrate the value cryo-imaging provides in the field of small animal imaging research.

  5. Transporting mouse embryos and germplasm as frozen or unfrozen materials.

    PubMed

    Kenyon, Janet; Guan, Mo; Bogani, Debora; Marschall, Susan; Raspa, Marcello; Pickard, Amanda; Takeo, Toru; Nakagata, Naomi; Fray, Martin

    2014-01-01

    The 21st century has seen a huge proliferation in the availability of genetically altered mice. The availability of these resources has been accompanied by ever greater opportunities for international collaborations between laboratories involving the exchange of mouse strains. This exchange can involve significant costs in terms of animal welfare and transportation expenses. In an attempt to mitigate some of these costs, the mouse community has developed a battery of techniques that can be used to avoid transporting live mice. Transporting frozen embryos and sperm at liquid nitrogen (LN2 ) temperatures using dry shippers has been common practice for some time. However, current advances in this field have refined transportation procedures and introduced new techniques for disseminating embryos and sperm: for example, shipping frozen sperm on dry ice, exchanging unfrozen epididymides from which sperm can be extracted, and transporting frozen/thawed embryos in isotonic media. This article discusses some of the current practices used by laboratories to transport mouse strains around the world without having to exchange live mice. PMID:25723918

  6. Mouse Sperm Cryopreservation and Recovery of Genetically Modified Mice.

    PubMed

    Low, Benjamin E; Taft, Rob A; Wiles, Michael V

    2016-01-01

    Highly definable genetically, the humble mouse is the "reagent" mammal of choice with which to probe and begin to understand the human condition in all its complexities. With the recent advance in direct genome editing via targeted nucleases, e.g., TALEN and CRISPR/Cas9, the possibilities in using these sophisticated tools have increased substantially leading to a massive increase in the variety of strain numbers of genetically modified lines. With this increase comes a greater need to economically and creatively manage their numbers. Further, once characterized, lines may be of limited use but still need to be archived in a format allowing their rapid resurrection. Further, maintaining colonies on "the shelf" is financially draining and carries potential risks including natural disaster loss, disease, and strain contamination. Here we outline a simple and economic protocol to cryopreserve mouse sperm from many different genetic backgrounds, and outline its recovery via in vitro fertilization (IVF). The combined use of sperm cryopreservation and IVF now allows a freedom and versatility in mouse management facilitating rapid line close down with the option to later recover and rapidly expand as needed. PMID:27150083

  7. Geodetic Strain Analysis Tool

    NASA Technical Reports Server (NTRS)

    Kedar, Sharon; Baxter, Sean C.; Parker, Jay W.; Webb, Frank H.; Owen, Susan E.; Sibthorpe, Anthony J.; Dong, Danan

    2011-01-01

    A geodetic software analysis tool enables the user to analyze 2D crustal strain from geodetic ground motion, and create models of crustal deformation using a graphical interface. Users can use any geodetic measurements of ground motion and derive the 2D crustal strain interactively. This software also provides a forward-modeling tool that calculates a geodetic velocity and strain field for a given fault model, and lets the user compare the modeled strain field with the strain field obtained from the user s data. Users may change parameters on-the-fly and obtain a real-time recalculation of the resulting strain field. Four data products are computed: maximum shear, dilatation, shear angle, and principal components. The current view and data dependencies are processed first. The remaining data products and views are then computed in a round-robin fashion to anticipate view changes. When an analysis or display parameter is changed, the affected data products and views are invalidated and progressively re-displayed as available. This software is designed to facilitate the derivation of the strain fields from the GPS and strain meter data that sample it to facilitate the understanding of the strengths and weaknesses of the strain field derivation from continuous GPS (CGPS) and other geodetic data from a variety of tectonic settings, to converge on the "best practices" strain derivation strategy for the Solid Earth Science ESDR System (SESES) project given the CGPS station distribution in the western U.S., and to provide SESES users with a scientific and educational tool to explore the strain field on their own with user-defined parameters.

  8. Decoding mechanisms of loss of fertilization ability of cryopreserved mouse sperm

    NASA Astrophysics Data System (ADS)

    Gray, Jeffrey Earl

    Cryopreservation of mouse sperm is an important technology for management of biomedical research resources. Dramatic progress has been made recently in the development of protocols that combat mouse-strain specific reduction of IVF after cryopreservation. Equal emphasis, however, has not been placed on investigating the biological mechanisms underlying these improvements to IVF. This dissertation broadly investigates the basic question of how mouse-strain specific reduction of IVF occurs after cryopreservation, and how recently developed protocols prevent this process. My research investigated the effects of antioxidants, the cholesterol-acceptor CD, reduced calcium media, and TYH capacitation media on sperm function and oxidative stress after cryopreservation in a variety of mouse strains. I found that reduced IVF was associated with loss of capacitation-dependent sperm function in three strains, B6/J, B6/N, and 129X1, and CD improved sperm function and IVF in all three strains. These findings suggest that cryopreservation inhibits cholesterol efflux resulting in reduced IVF of many mouse strains. I also found that cryopreservation induces uniquely high production of mitochondrial H2O2 by B6/J sperm. H2O2 present in other cellular compartments of B6/J sperm was not elevated compared to other strains. High levels of mitochondrial H2O2 were associated with lipid peroxidation of the sperm head and inability to acrosome react. Antioxidants reduced mitochondrial H2O2 production, decreased sperm head lipid peroxidation, and improved acrosome reaction. The cryopreservation-induced increase in mitochondrial H2O2 production of B6/J and B6129XF1 sperm was associated with elevation of intracellular calcium after cryopreservation and dependent on mitochondrial metabolic substrates. Reducing intracellular calcium levels or removing mitochondrial metabolic substrates decreased mitochondrial H2O2 production and increased IVF rates of cryopreserved B6/J sperm. Many of the strains

  9. Transgenic Mouse Model of Chronic Beryllium Disease

    SciTech Connect

    Gordon, Terry

    2009-05-26

    Animal models provide powerful tools for dissecting dose-response relationships and pathogenic mechanisms and for testing new treatment paradigms. Mechanistic research on beryllium exposure-disease relationships is severely limited by a general inability to develop a sufficient chronic beryllium disease animal model. Discovery of the Human Leukocyte Antigen (HLA) - DPB1Glu69 genetic susceptibility component of chronic beryllium disease permitted the addition of this human beryllium antigen presentation molecule to an animal genome which may permit development of a better animal model for chronic beryllium disease. Using FVB/N inbred mice, Drs. Rubin and Zhu, successfully produced three strains of HLA-DPB1 Glu 69 transgenic mice. Each mouse strain contains a haplotype of the HLA-DPB1 Glu 69 gene that confers a different magnitude of odds ratio (OR) of risk for chronic beryllium disease: HLA-DPB1*0401 (OR = 0.2), HLA-DPB1*0201 (OR = 15), HLA-DPB1*1701 (OR = 240). In addition, Drs. Rubin and Zhu developed transgenic mice with the human CD4 gene to permit better transmission of signals between T cells and antigen presenting cells. This project has maintained the colonies of these transgenic mice and tested the functionality of the human transgenes.

  10. Tympanometry Assessment of 61 Inbred Strains of Mice

    PubMed Central

    Zheng, Qing Yin; Tong, Yi-Cai Isaac; Alagramam, Kumar N.; Yu, Heping

    2007-01-01

    Otitis Media (OM) accounts for more than 20 million clinic visits in the United States every year. Resistance to antibiotics has hampered current management of the disease. Identification of genetic factors underlying susceptibility to OM is greatly needed in order to develop alternative treatment strategies. Genetically defined inbred mouse strains offer a powerful tool for dissecting genetic and environmental factors that may lead to OM in mice. Here we report a study of middle ear function of 61 genetically diverse inbred strains of mice using tympanometry. Of the 61 inbred strains tested, the 129P1/ReJ, 129P3/J, 129S1/SvImJ, 129X1/SvJ, A/HeJ, BALB/cJ, BUB/BnJ, C57L/J, EL/SuzSeyFrkJ, FVB/NJ, I/LnJ, LP/J, NZB/BlNJ, PL/J and YBR/Ei strains exhibited tympanograms that were statistically different from other healthy strains according to parameters including middle ear pressure, volume and compliance. These differences are most likely the result of genetic factors that, when understood, will facilitate prevention and treatment of otitis media in humans. In addition, a negative correlation between age and compliance of the tympanic membrane was discovered. This is the first report to successfully use tympanometry to measure mouse middle ear function, which has been a challenge for the hearing research field because of the mouse’s tiny ear size. PMID:17611057

  11. Preclinical mouse models of osteosarcoma.

    PubMed

    Uluçkan, Özge; Segaliny, Aude; Botter, Sander; Santiago, Janice M; Mutsaers, Anthony J

    2015-01-01

    Osteosarcoma is the most common form of primary bone tumors with high prevalence in children. Survival rates of osteosarcoma are low, especially in the case of metastases. Mouse models of this disease have been very valuable in investigation of mechanisms of tumorigenesis, metastasis, as well as testing possible therapeutic options. In this chapter, we summarize currently available mouse models for osteosarcoma and provide detailed methodology for the isolation of cell lines from genetically engineered mouse models (GEMMs), gene modification and tumor cell injection methods, as well as imaging techniques. PMID:25987985

  12. Blastocyst genotyping for quality control of mouse mutant archives: an ethical and economical approach.

    PubMed

    Scavizzi, Ferdinando; Ryder, Edward; Newman, Stuart; Raspa, Marcello; Gleeson, Diane; Wardle-Jones, Hannah; Montoliu, Lluis; Fernandez, Almudena; Dessain, Marie-Laure; Larrigaldie, Vanessa; Khorshidi, Zuzana; Vuolteenaho, Reetta; Soininen, Raija; André, Philippe; Jacquot, Sylvie; Hong, Yi; de Angelis, Martin Hrabe; Ramirez-Solis, Ramiro; Doe, Brendan

    2015-10-01

    With the advent of modern developmental biology and molecular genetics, the scientific community has generated thousands of newly genetically altered strains of laboratory mice with the aim of elucidating gene function. To this end, a large group of Institutions which form the International Mouse Phenotyping Consortium is generating and phenotyping a knockout mouse strain for each of the ~20,000 protein-coding genes using the mutant ES cell resource produced by the International Knockout Mouse Consortium. These strains are made available to the research community via public repositories, mostly as cryopreserved sperm or embryos. To ensure the quality of this frozen resource there is a requirement that for each strain the frozen sperm/embryos are proven able to produce viable mutant progeny, before the live animal resource is removed from cages. Given the current requirement to generate live pups to demonstrate their mutant genotype, this quality control check necessitates the use and generation of many animals and requires considerable time, cage space, technical and economic resources. Here, we describe a simple and efficient method of genotyping pre-implantation stage blastocysts with significant ethical and economic advantages especially beneficial for current and future large-scale mouse mutagenesis projects. PMID:26178246

  13. Mechanical strain isolator mount

    NASA Technical Reports Server (NTRS)

    James, Gordon E. (Inventor)

    1991-01-01

    Certain devices such as optical instruments must preserve their alignmental integrity while being subjected to mechanical strain. A mechanical strain isolator mount is provided to preserve the alignmental integrity of an alignment sensitive instrument. An alignment sensitive instrument is mounted on a rectangular base. Flexural legs are connected at their proximal ends to the rectangular base. Flexural legs are also spaced parallel to the sides. Mounting pads are connected to the legs at the distal end and the mechanical strain isolator mount is attached to the substrate by means of threaded bolts. When a mounting pad and its respective leg is subjected to lateral strain in either the X or Y direction via the substrate, the respective leg relieves the strain by bending in the direction of the strain. An axial strain on a mounting pad in the Z direction is relieved by a rotational motion of the legs in the direction of the strain. When the substrate is stress free, the flexural legs return to their original condition and thus preserve the original alignment integrity of the alignment sensitive instrument.

  14. Light intensity strain analysis

    NASA Technical Reports Server (NTRS)

    Williams, J. G. (Inventor)

    1973-01-01

    A process is described for the analysis of the strain field of structures subjected to large deformations involving a low modulus substrate having a high modulus, relatively thin coating. The optical properties of transmittance and reflectance are measured for the coated substrate while stressed and unstressed to indicate the strain field for the coated substrate.

  15. The mouse "xenotropic" gammaretroviruses and their XPR1 receptor

    PubMed Central

    2010-01-01

    The xenotropic/polytropic subgroup of mouse leukemia viruses (MLVs) all rely on the XPR1 receptor for entry, but these viruses vary in tropism, distribution among wild and laboratory mice, pathogenicity, strategies used for transmission, and sensitivity to host restriction factors. Most, but not all, isolates have typical xenotropic or polytropic host range, and these two MLV tropism types have now been detected in humans as viral sequences or as infectious virus, termed XMRV, or xenotropic murine leukemia virus-related virus. The mouse xenotropic MLVs (X-MLVs) were originally defined by their inability to infect cells of their natural mouse hosts. It is now clear, however, that X-MLVs actually have the broadest host range of the MLVs. Nearly all nonrodent mammals are susceptible to X-MLVs, and all species of wild mice and several common strains of laboratory mice are X-MLV susceptible. The polytropic MLVs, named for their apparent broad host range, show a more limited host range than the X-MLVs in that they fail to infect cells of many mouse species as well as many nonrodent mammals. The co-evolution of these viruses with their receptor and other host factors that affect their replication has produced a heterogeneous group of viruses capable of inducing various diseases, as well as endogenized viral genomes, some of which have been domesticated by their hosts to serve in antiviral defense. PMID:21118532

  16. Mouse genotypes drive the liver and adrenal gland clocks.

    PubMed

    Košir, Rok; Prosenc Zmrzljak, Uršula; Korenčič, Anja; Juvan, Peter; Ačimovič, Jure; Rozman, Damjana

    2016-01-01

    Circadian rhythms regulate a plethora of physiological processes. Perturbations of the rhythm can result in pathologies which are frequently studied in inbred mouse strains. We show that the genotype of mouse lines defines the circadian gene expression patterns. Expression of majority of core clock and output metabolic genes are phase delayed in the C56BL/6J line compared to 129S2 in the adrenal glands and the liver. Circadian amplitudes are generally higher in the 129S2 line. Experiments in dark - dark (DD) and light - dark conditions (LD), exome sequencing and data mining proposed that mouse lines differ in single nucleotide variants in the binding regions of clock related transcription factors in open chromatin regions. A possible mechanisms of differential circadian expression could be the entrainment and transmission of the light signal to peripheral organs. This is supported by the genotype effect in adrenal glands that is largest under LD, and by the high number of single nucleotide variants in the Receptor, Kinase and G-protein coupled receptor Panther molecular function categories. Different phenotypes of the two mouse lines and changed amino acid sequence of the Period 2 protein possibly contribute further to the observed differences in circadian gene expression. PMID:27535584

  17. Mouse genotypes drive the liver and adrenal gland clocks

    PubMed Central

    Košir, Rok; Prosenc Zmrzljak, Uršula; Korenčič, Anja; Juvan, Peter; Ačimovič, Jure; Rozman, Damjana

    2016-01-01

    Circadian rhythms regulate a plethora of physiological processes. Perturbations of the rhythm can result in pathologies which are frequently studied in inbred mouse strains. We show that the genotype of mouse lines defines the circadian gene expression patterns. Expression of majority of core clock and output metabolic genes are phase delayed in the C56BL/6J line compared to 129S2 in the adrenal glands and the liver. Circadian amplitudes are generally higher in the 129S2 line. Experiments in dark – dark (DD) and light – dark conditions (LD), exome sequencing and data mining proposed that mouse lines differ in single nucleotide variants in the binding regions of clock related transcription factors in open chromatin regions. A possible mechanisms of differential circadian expression could be the entrainment and transmission of the light signal to peripheral organs. This is supported by the genotype effect in adrenal glands that is largest under LD, and by the high number of single nucleotide variants in the Receptor, Kinase and G-protein coupled receptor Panther molecular function categories. Different phenotypes of the two mouse lines and changed amino acid sequence of the Period 2 protein possibly contribute further to the observed differences in circadian gene expression. PMID:27535584

  18. Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

    PubMed Central

    Rakoczy, Elizabeth P.; Rahman, Ireni S. Ali; Binz, Nicolette; Li, Cai-Rui; Vagaja, Nermina N.; de Pinho, Marisa; Lai, Chooi-May

    2010-01-01

    One of the limitations of research into diabetic retinopathy is the lack of suitable animal models. To study how the two important factors—hyperglycemia and vascular endothelial growth factor—interact in diabetic retinopathy, the Akimba mouse (Ins2AkitaVEGF+/−) was generated by crossing the Akita mouse (Ins2Akita) with the Kimba mouse (VEGF+/+). C57Bl/6 and the parental and Akimba mouse lines were characterized by biometric measurements, histology, immunohistochemistry, and Spectralis Heidelberg retinal angiography and optical coherence tomography. The Akimba line not only retained the characteristics of the parental strains, such as developing hyperglycemia and retinal neovascularization, but developed higher blood glucose levels at a younger age and had worse kidney-body weight ratios than the Akita line. With aging, the Akimba line demonstrated enhanced photoreceptor cell loss, thinning of the retina, and more severe retinal vascular pathology, including more severe capillary nonperfusion, vessel constriction, beading, neovascularization, fibroses, and edema, compared with the Kimba line. The vascular changes were associated with major histocompatibility complex class II+ cellular staining throughout the retina. Together, these observations suggest that hyperglycemia resulted in higher prevalences of edema and exacerbated the vascular endothelial growth factor-driven neovascular and retinal changes in the Akimba line. Thus, the Akimba line could become a useful model for studying the interplay between hyperglycemia and vascular endothelial growth factor and for testing treatment strategies for potentially blinding complications, such as edema. PMID:20829433

  19. Novel object exploration in the C58/J mouse model of autistic-like behavior.

    PubMed

    Blick, Mikkal G; Puchalski, Breann H; Bolanos, Veronica J; Wolfe, Kaitlin M; Green, Matthew C; Ryan, Bryce C

    2015-04-01

    Mouse models of autistic like behaviors are a valuable tool to use when studying the causes, symptoms, and potential treatments for autism. The inbred C58/J strain is a strain of interest for this model and has previously been shown to possess face validity for some of the core traits of autism, including low social behavior and elevated motor stereotypies. Higher order repetitive behaviors have not been extensively studied in this strain, or in mice in general. In this study, we looked for evidence of higher-order repetitive behaviors in the C58/J strain using a novel object assay. This assay utilized a mouse's natural exploratory behavior among unfamiliar objects to identify potential sequencing patterns in motor activity. The motor stereotypies displayed by the C58/J strain during testing were consistent with past studies. The C58/J strain also displayed a high preference for a single object in the round arena assays and the females demonstrating elevated sequencing patterns in the round arena. Although the C58/J strain did not show pervasive evidence of higher-order repetitive behaviors across all measures, there was evidence of higher order repetitive behaviors in certain situations. This study further demonstrates the potential of the C58/J mouse strains as a model for lower-order and potentially, higher-order repetitive behaviors. This study also demonstrates that the shape of the novel object arena can change the behavior displayed by the test animals. Further studies utilizing the C58/J strain and further validation of the novel object assay are warranted. PMID:25532914

  20. Cryptococcus Strains with Different Pathogenic Potentials Have Diverse Protein Secretomes

    PubMed Central

    Campbell, Leona T.; Simonin, Anna R.; Chen, Cuilan; Ferdous, Jannatul; Padula, Matthew P.; Harry, Elizabeth; Hofer, Markus; Campbell, Iain L.

    2015-01-01

    Secreted proteins are the frontline between the host and pathogen. In mammalian hosts, secreted proteins enable invasive infection and can modulate the host immune response. Cryptococcosis, caused by pathogenic Cryptococcus species, begins when inhaled infectious propagules establish to produce pulmonary infection, which, if not resolved, can disseminate to the central nervous system to cause meningoencephalitis. Strains of Cryptococcus species differ in their capacity to cause disease, and the mechanisms underlying this are not well understood. To investigate the role of secreted proteins in disease, we determined the secretome for three genome strains of Cryptococcus species, including a hypovirulent and a hypervirulent strain of C. gattii and a virulent strain of C. neoformans. Sixty-seven unique proteins were identified, with different numbers and types of proteins secreted by each strain. The secretomes of the virulent strains were largely limited to proteolytic and hydrolytic enzymes, while the hypovirulent strain had a diverse secretome, including non-conventionally secreted canonical cytosolic and immunogenic proteins that have been implicated in virulence. The hypovirulent strain cannot establish pulmonary infection in a mouse model, but strains of this genotype have caused human meningitis. To directly test brain infection, we used intracranial inoculation and found that the hypovirulent strain was substantially more invasive than its hypervirulent counterpart. We suggest that immunogenic proteins secreted by this strain invoke a host response that limits pulmonary infection but that there can be invasive growth and damage if infection reaches the brain. Given their known role in virulence, it is possible that non-conventionally secreted proteins mediate this process. PMID:25841021

  1. Computer Workstation: Pointer/Mouse

    MedlinePlus

    ... and long term use. Potential Hazards: When the sensitivity for the input device is not appropriately set, ... provide adequate control. A mouse that has insufficient sensitivity may require large deviation of the wrist to ...

  2. GXD: a Gene Expression Database for the laboratory mouse: current status and recent enhancements

    PubMed Central

    Ringwald, Martin; Eppig, Janan T.; Kadin, James A.; Richardson, Joel E.; the Gene Expression Database Group

    2000-01-01

    The Gene Expression Database (GXD) is a community resource of gene expression information for the laboratory mouse. The database is designed as an open-ended system that can integrate different types of expression data. New expression data are made available on a daily basis. Thus, GXD provides increasingly complete information about what transcripts and proteins are produced by what genes; where, when and in what amounts these gene products are expressed; and how their expression varies in different mouse strains and mutants. GXD is integrated with the Mouse Genome Database (MGD). Continuously refined interconnections with sequence databases and with databases from other species place the gene expression information in the larger biological and analytical context. GXD is accessible through the Mouse Genome Informatics Web site at http://www. informatics.jax.org/ or directly at http://www.informatics. jax.org/menus/expression_menu.shtml PMID:10592197

  3. In vivo characterization of two additional Leishmania donovani strains using the murine and hamster model.

    PubMed

    Kauffmann, F; Dumetz, F; Hendrickx, S; Muraille, E; Dujardin, J-C; Maes, L; Magez, S; De Trez, C

    2016-05-01

    Leishmania donovani is a protozoan parasite causing the neglected tropical disease visceral leishmaniasis. One difficulty to study the immunopathology upon L. donovani infection is the limited adaptability of the strains to experimental mammalian hosts. Our knowledge about L. donovani infections relies on a restricted number of East African strains (LV9, 1S). Isolated from patients in the 1960s, these strains were described extensively in mice and Syrian hamsters and have consequently become 'reference' laboratory strains. L. donovani strains from the Indian continent display distinct clinical features compared to East African strains. Some reports describing the in vivo immunopathology of strains from the Indian continent exist. This study comprises a comprehensive immunopathological characterization upon infection with two additional strains, the Ethiopian L. donovani L82 strain and the Nepalese L. donovani BPK282 strain in both Syrian hamsters and C57BL/6 mice. Parameters that include parasitaemia levels, weight loss, hepatosplenomegaly and alterations in cellular composition of the spleen and liver, showed that the L82 strain generated an overall more virulent infection compared to the BPK282 strain. Altogether, both L. donovani strains are suitable and interesting for subsequent in vivo investigation of visceral leishmaniasis in the Syrian hamster and the C57BL/6 mouse model. PMID:27012562

  4. Differences in lymphomagenic properties of AKR mouse retroviruses.

    PubMed

    Hays, E F; Levy, J A

    1984-10-15

    Long-term studies on lymphomagenicity of several AKR mouse retroviruses have shown that the biologically cloned ecotropic SL3-3c virus is the most lymphomagenic of all viruses tested. This fact was demonstrated by lymphomagenicity in five mouse strains SJL, C3Hf/Bi, C3H/HeJ, CBA/H, and NFS, and lymphoma acceleration in AKR mice. The incidence was higher and latent periods shorter than that found with the other retroviruses tested (SL3-1c, SL3-2c, MCFc, and GMuLVc). In addition, it was the only retrovirus found to be highly oncogenic in the C3H/HeJ and CBA/H strains. Lack of lymphomagenicity of MCFc in CBA/H strain was shown to be due to a block in viral replication. Addition of nononcogenic Akv ecotropic virus did not affect this lack of oncogenicity. The lymphomas developing in CBA/H and SJL mice after neonatal inoculation of SL3-3c virus only produced lymphomagenic ecotropic virus. Thus, SL3-3c lymphomagenesis is most likely due solely to the action of that virus. These studies indicate that pure ecotropic AKR viruses can be highly leukemogenic. PMID:6093361

  5. MPTP Mouse Models of Parkinson’s Disease: An Update

    PubMed Central

    Meredith, Gloria E.; Rademacher, David J.

    2012-01-01

    Among the most widely used models of Parkinson’s disease (PD) are those that employ toxins, especially 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Depending on the protocol used, MPTP yields large variations in nigral cell loss, striatal dopamine loss and behavioral deficits. Motor deficits do not fully replicate those seen in PD. Nonetheless, MPTP mouse models mimic many aspects of the disease and are therefore important tools for understanding PD. In this review, we will discuss the ability of MPTP mouse models to replicate the pathophysiology of PD, the mechanisms of MPTP-induced neurotoxicity, strain differences in susceptibility to MPTP, and the models’ roles in testing therapeutic approaches. PMID:23275799

  6. Prolonged in vitro closure of the mouse secondary palate by salicylates.

    PubMed

    Saxén, I

    1975-07-01

    In organ culture sodium salicylate and acetylsalicylic acid in a 1.4 mM concentration caused prolongation of the time needed for the closure of the mouse secondary palate. The response of Strain A and the hybrids CBA X A was more distinct than that of Strain CBA. The mitotic rate, calculated from serial sections, was significantly reduced in the salicylate-treated shelves in both strains. The extrapolation of the results to an in vivo situation is discussed in the light of different theories of the mechanism of cleft palate formation. PMID:1057785

  7. Recovery of a strain of Clostridium botulinum producing both neurotoxin A and neurotoxin B from canned macrobiotic food.

    PubMed

    Franciosa, G; Fenicia, L; Pourshaban, M; Aureli, P

    1997-03-01

    A rare strain of Clostridium botulinum subtype Ab was isolated from a canned macrobiotic food suspected of being linked to a fatal case of food-borne botulism. The strain was recovered and identified by conventional methods modified by the inclusion of a PCR assay (G. Franciosa, J.L. Ferreira, and C.L. Hatheway, J. Clin. Microbiol. 32:1911-1917, 1994). The titers of neurotoxins produced by the strain were evaluated by a mouse bioassay. PMID:9055430

  8. Recovery of a strain of Clostridium botulinum producing both neurotoxin A and neurotoxin B from canned macrobiotic food.

    PubMed Central

    Franciosa, G; Fenicia, L; Pourshaban, M; Aureli, P

    1997-01-01

    A rare strain of Clostridium botulinum subtype Ab was isolated from a canned macrobiotic food suspected of being linked to a fatal case of food-borne botulism. The strain was recovered and identified by conventional methods modified by the inclusion of a PCR assay (G. Franciosa, J.L. Ferreira, and C.L. Hatheway, J. Clin. Microbiol. 32:1911-1917, 1994). The titers of neurotoxins produced by the strain were evaluated by a mouse bioassay. PMID:9055430

  9. Determination of Three-Dimensional Ventricular Strain Distributions in Gene-Targeted Mice Using Tagged MRI

    PubMed Central

    Chuang, Joyce S.; Zemljic-Harpf, Alice; Ross, Robert S.; Frank, Lawrence R.; McCulloch, Andrew D.; Omens, Jeffrey H.

    2012-01-01

    A model-based method for calculating three-dimensional (3D) cardiac wall strain distributions in the mouse has been developed and tested in a genetically engineered mouse model of dilated cardiomyopathy. Data from MR tagging and harmonic phase (HARP) tracking were used to measure material point displacements, and 3D Lagrangian strains were calculated throughout the entire left ventricle (LV) with a deformable parametric model. A mouse model where cardiomyocytes are specifically made deficient in vinculin (VclKO) were compared to wild-type (WT) littermates. 3D strain analysis revealed differences in LV wall mechanics between WT and VclKO mice at 8 weeks of age when systolic function had just begun to decline. Most notably, end-systolic radial strain and torsional shear were reduced in VclKO hearts which contributed to regional mechanical dysfunction. This study demonstrates the feasibility of using MRI tagging methods to detect alterations in 3D myocardial strain distributions in genetically engineered mouse models of cardiovascular disease. PMID:20981782

  10. Cells as strain-cued automata

    NASA Astrophysics Data System (ADS)

    Cox, Brian N.; Snead, Malcolm L.

    2016-02-01

    We argue in favor of representing living cells as automata and review demonstrations that autonomous cells can form patterns by responding to local variations in the strain fields that arise from their individual or collective motions. An autonomous cell's response to strain stimuli is assumed to be effected by internally-generated, internally-powered forces, which generally move the cell in directions other than those implied by external energy gradients. Evidence of cells acting as strain-cued automata have been inferred from patterns observed in nature and from experiments conducted in vitro. Simulations that mimic particular cases of pattern forming share the idealization that cells are assumed to pass information among themselves solely via mechanical boundary conditions, i.e., the tractions and displacements present at their membranes. This assumption opens three mechanisms for pattern formation in large cell populations: wavelike behavior, kinematic feedback in cell motility that can lead to sliding and rotational patterns, and directed migration during invasions. Wavelike behavior among ameloblast cells during amelogenesis (the formation of dental enamel) has been inferred from enamel microstructure, while strain waves in populations of epithelial cells have been observed in vitro. One hypothesized kinematic feedback mechanism, "enhanced shear motility", accounts successfully for the spontaneous formation of layered patterns during amelogenesis in the mouse incisor. Directed migration is exemplified by a theory of invader cells that sense and respond to the strains they themselves create in the host population as they invade it: analysis shows that the strain fields contain positional information that could aid the formation of cell network structures, stabilizing the slender geometry of branches and helping govern the frequency of branch bifurcation and branch coalescence (the formation of closed networks). In simulations of pattern formation in

  11. Mouse genetic approaches applied to the normal tissue radiation response

    PubMed Central

    Haston, Christina K.

    2012-01-01

    The varying responses of inbred mouse models to radiation exposure present a unique opportunity to dissect the genetic basis of radiation sensitivity and tissue injury. Such studies are complementary to human association studies as they permit both the analysis of clinical features of disease, and of specific variants associated with its presentation, in a controlled environment. Herein I review how animal models are studied to identify specific genetic variants influencing predisposition to radiation-induced traits. Among these radiation-induced responses are documented strain differences in repair of DNA damage and in extent of tissue injury (in the lung, skin, and intestine) which form the base for genetic investigations. For example, radiation-induced DNA damage is consistently greater in tissues from BALB/cJ mice, than the levels in C57BL/6J mice, suggesting there may be an inherent DNA damage level per strain. Regarding tissue injury, strain specific inflammatory and fibrotic phenotypes have been documented for principally, C57BL/6 C3H and A/J mice but a correlation among responses such that knowledge of the radiation injury in one tissue informs of the response in another is not evident. Strategies to identify genetic differences contributing to a trait based on inbred strain differences, which include linkage analysis and the evaluation of recombinant congenic (RC) strains, are presented, with a focus on the lung response to irradiation which is the only radiation-induced tissue injury mapped to date. Such approaches are needed to reveal genetic differences in susceptibility to radiation injury, and also to provide a context for the effects of specific genetic variation uncovered in anticipated clinical association studies. In summary, mouse models can be studied to uncover heritable variation predisposing to specific radiation responses, and such variations may point to pathways of importance to phenotype development in the clinic. PMID:22891164

  12. Detection of a large RIII-derived chromosomal segment on chromosome 10 in the H-2 congenic strain B10.RIII(71NS)/Sn

    SciTech Connect

    Dong, P.; Hood, L.; McIndoe, R.A.

    1996-01-15

    This report describes the results of a study of the chromosomal localization of certain loci related to the susceptibility of specific mouse strains to collagen-induced arthritis, the biological model for rheumatoid arthritis. There were surprising results concerning the chromosomal mapping of mouse chromosome 10 and 17 and the backcrosses of mice involved. 7 refs., 1 fig., 2 tabs.

  13. Deformation measurements and material property estimation of mouse carotid artery using a microstructure-based constitutive model.

    PubMed

    Ning, Jinfeng; Xu, Shaowen; Wang, Ying; Lessner, Susan M; Sutton, Michael A; Anderson, Kevin; Bischoff, Jeffrey E

    2010-12-01

    A series of pressurization and tensile loading experiments on mouse carotid arteries is performed with deformation measurements acquired during each experiment using three-dimensional digital image correlation. Using a combination of finite element analysis and a microstructure-based constitutive model to describe the response of biological tissue, the measured surface strains during pressurization, and the average axial strains during tensile loading, an inverse procedure is used to identify the optimal constitutive parameters for the mouse carotid artery. The results demonstrate that surface strain measurements can be combined with computational methods to identify material properties in a vascular tissue. Additional computational studies using the optimal material parameters for the mouse carotid artery are discussed with emphasis on the significance of the qualitative trends observed. PMID:21142324

  14. Genome Wide Analysis of Inbred Mouse Lines Identifies a Locus Containing Ppar-γ as Contributing to Enhanced Malaria Survival

    PubMed Central

    Henson, Kerstin; Luzader, Angelina; Lindstrom, Merle; Spooner, Muriel; Steffy, Brian M.; Suzuki, Oscar; Janse, Chris; Waters, Andrew P.; Zhou, Yingyao; Wiltshire, Tim; Winzeler, Elizabeth A.

    2010-01-01

    The genetic background of a patient determines in part if a person develops a mild form of malaria and recovers, or develops a severe form and dies. We have used a mouse model to detect genes involved in the resistance or susceptibility to Plasmodium berghei malaria infection. To this end we first characterized 32 different mouse strains infected with P. berghei and identified survival as the best trait to discriminate between the strains. We found a locus on chromosome 6 by linking the survival phenotypes of the mouse strains to their genetic variations using genome wide analyses such as haplotype associated mapping and the efficient mixed-model for association. This new locus involved in malaria resistance contains only two genes and confirms the importance of Ppar-γ in malaria infection. PMID:20531941

  15. Single Targeted Exon Mutation Creates a True Congenic Mouse for Competitive Hematopoietic Stem Cell Transplantation: The C57BL/6-CD45.1(STEM) Mouse.

    PubMed

    Mercier, Francois E; Sykes, David B; Scadden, David T

    2016-06-14

    Defining the molecular regulators of hematopoietic stem and progenitor cells (HSPCs) requires in vivo functional analyses. Competitive bone marrow transplants (BMTs) compare control and test HSPCs to demonstrate the functional role of a genetic change or chemical perturbation. Competitive BMT is enabled by antibodies that specifically recognize hematopoietic cells from congenic mouse strains due to variants of the cell surface protein CD45, designated CD45.1 and CD45.2. The current congenic competitor strain, B6.SJL-Ptprc(a) Pepc(b)/BoyJ (CD45.1), has a substantial inherent disadvantage in competition against the C57BL/6 (CD45.2) strain, confounding experimental interpretation. Despite backcrossing, the congenic interval over which the B6.SJL-Ptprc(a) Pepc(b)/BoyJ strain differs is almost 40 Mb encoding ∼300 genes. Here, we demonstrate that a single amino acid change determines the CD45.1 epitope. Further, we report on the single targeted exon mutant (STEM) mouse strain, CD45.1(STEM), which is functionally equivalent to CD45.2 cells in competitive BMT. This strain will permit the precise definition of functional roles for candidate genes using in vivo HSPC assays. PMID:27185283

  16. Strain gauge installation tool

    DOEpatents

    Conard, Lisa Marie

    1998-01-01

    A tool and a method for attaching a strain gauge to a test specimen by maaining alignment of, and applying pressure to, the strain gauge during the bonding of the gauge to the specimen. The tool comprises rigid and compliant pads attached to a spring-loaded clamp. The pads are shaped to conform to the specimen surface to which the gauge is to be bonded. The shape of the pads permits the tool to align itself to the specimen and to maintain alignment of the gauge to the specimen during the bond curing process. A simplified method of attaching a strain gauge is provided by use of the tool.

  17. Mechanochromic polyurethane strain sensor

    NASA Astrophysics Data System (ADS)

    Cellini, F.; Khapli, S.; Peterson, S. D.; Porfiri, M.

    2014-08-01

    In this Letter, we study the mechanical and optical response of a thermoplastic polyurethane blended with 0.5 wt. % of bis(benzoxazolyl)stilbene dye. The mechanochromic behavior of the material is characterized in a uniaxial stress-relaxation test by simultaneously acquiring the applied force, mechanical deformation, and fluorescence emission. To offer insight into the stress-strain response of the polymer-dye blend, we adapt a classical nonlinear constitutive behavior for elastomeric materials that accounts for stress-induced softening. We correlate the fluorescent response with the mechanical strain to demonstrate the possibility of accurate strain sensing for a broad range of deformations during both loading and unloading.

  18. Strain gauge installation tool

    SciTech Connect

    Conard, Lisa Marie

    1997-12-01

    A tool and a method for attaching a strain gauge to a test specimen by maintaining alignment of, and applying pressure to, the strain gauge during the bonding of the gauge to the specimen. The tool comprises rigid and compliant pads attached to a spring-loaded clamp. The pads are shaped to conform to the specimen surface to which the gauge is to be bonded. The shape of the pads permits the tool to align itself to the specimen and to maintain alignment of the gauge to the specimen during the bond curing process. A simplified method of attaching a strain gauge is provided by use of the tool.

  19. Characterization of gait and olfactory behaviors in the Balb/c mouse model of autism spectrum disorders.

    PubMed

    Burket, Jessica A; Young, Chelsea M; Green, Torrian L; Benson, Andrew D; Deutsch, Stephen I

    2016-04-01

    Abnormalities of gait and olfaction have been reported in persons with autism spectrum disorders (ASDs), which could reflect involvement of the cerebellum and nodes related to olfaction (e.g., olfactory bulb and ventral temporal olfactory cortex) in neural circuits subserving social, cognitive, and motor domains of psychopathology in these disorders. We hypothesized that the Balb/c mouse model of ASD would express "abnormalities" of gait and olfaction, relative to the Swiss Webster comparator strain. Contrary to expectation, Balb/c and Swiss Webster mice did not differ in terms of quantitative measurements of gait and mouse rotarod behavior, and Balb/c mice displayed a shorter latency to approach an unscented cotton swab, suggesting that there was no disturbance of its locomotor behavior. However, Balb/c mice showed significant inhibition of locomotor activity in the presence of floral scents, including novel and familiar floral scents, and a socially salient odor (i.e., concentrated mouse urine); the inhibitory effect on the locomotor behavior of the Balb/c mouse was especially pronounced with the salient social odor. Unlike the Swiss Webster strain, mouse urine lacks social salience for the Balb/c mouse strain, a model of ASD, which does not appear to be an artifact of diminished olfactory sensitivity or impaired locomotion. PMID:26917431

  20. Antigens of Bordetella pertussis V. Separation of Agglutinogen 1 and Mouse-Protective Antigen.

    PubMed

    Ross, R F; Munoz, J

    1971-02-01

    Agglutinogen 1 of Bordetella pertussis strain 353/Z (serotype 1) was separated from protective antigen and histamine-sensitizing factor by starch-block electrophoresis. Most of the agglutinogen 1 migrated towards the cathode in starch-block electrophoresis, although some remained near the origin. Fractions containing most of the agglutinogen 1 were free of detectable mouse-protecting or histamine-sensitizing activities. Agglutinogen 1 from a serotype 1, 3 B. pertussis strain (J20) migrated similarly to the agglutinogen 1 from strain 353/Z. All agglutinogen 3 activity was found at the point of application in the starch block. No clear relationship was found between agglutinogen 1 and mouse-protecting antigen or histamine-sensitizing factor. PMID:16557960

  1. Antigens of Bordetella pertussis V. Separation of Agglutinogen 1 and Mouse-Protective Antigen

    PubMed Central

    Ross, R. F.; Munoz, J.

    1971-01-01

    Agglutinogen 1 of Bordetella pertussis strain 353/Z (serotype 1) was separated from protective antigen and histamine-sensitizing factor by starch-block electrophoresis. Most of the agglutinogen 1 migrated towards the cathode in starch-block electrophoresis, although some remained near the origin. Fractions containing most of the agglutinogen 1 were free of detectable mouse-protecting or histamine-sensitizing activities. Agglutinogen 1 from a serotype 1, 3 B. pertussis strain (J20) migrated similarly to the agglutinogen 1 from strain 353/Z. All agglutinogen 3 activity was found at the point of application in the starch block. No clear relationship was found between agglutinogen 1 and mouse-protecting antigen or histamine-sensitizing factor. Images PMID:16557960

  2. Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study.

    PubMed

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2016-07-25

    Molecular epidemiological data indicates that the resurgence of pertussis (whooping cough) in populations with high vaccine coverage is associated with genomic adaptation of Bordetella pertussis, the causative agent of the disease, to vaccine selection pressure. We have previously shown that in the period after the introduction of acellular pertussis vaccine (ACV), the majority of circulating strains in Australia switched to single nucleotide polymorphism (SNP) cluster I (carrying ptxP3/prn2), replacing SNP cluster II (carrying ptxP1/prn3). In this study, we carried out an in vivo competition assay using a mouse model infected with SNP cluster I and II B. pertussis strains from Australia. We found that the SNP cluster I strain colonised better than the SNP cluster II strain, in both naïve and immunised mice, suggesting that SNP cluster I strains had better fitness regardless of immunisation status of the host, consistent with SNP cluster I strains replacing SNP cluster II. Nevertheless, we found that ACV enhanced clearance of both SNP cluster I and II strains from the mouse respiratory tract. PMID:27346304

  3. Chronic Myeloid Leukemia (CML) Mouse Model in Translational Research.

    PubMed

    Peng, Cong; Li, Shaoguang

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of granulocytic cells without the loss of their capability to differentiate. CML is a clonal disease, originated at the level of Hematopoietic Stem Cells with the Philadelphia chromosome resulting from a reciprocal translocation between the chromosomes 9 and 22t(9;22)-(q34;q11). This translocation produces a fusion gene known as BCR-ABL which acquires uncontrolled tyrosine kinase activity, constantly turning on its downstream signaling molecules/pathways, and promoting proliferation of leukemia cell through anti-apoptosis and acquisition of additional mutations. To evaluate the role of each critical downstream signaling molecule of BCR-ABL and test therapeutic drugs in vivo, it is important to use physiological mouse disease models. Here, we describe a mouse model of CML induced by BCR-ABL retrovirus (MSCV-BCR-ABL-GFP; MIG-BCR-ABL) and how to use this model in translational research.Moreover, to expand the application of this retrovirus induced CML model in a lot of conditional knockout mouse strain, we modified this vector to a triple gene coexpression vector in which we can co-express BCR-ABL, GFP, and a third gene which will be tested in different systems. To apply this triple gene system in conditional gene knockout strains, we can validate the CML development in the knockout mice and trace the leukemia cell following the GFP marker. In this protocol, we also describe how we utilize this triple gene system to prove the function of Pten as a tumor suppressor in leukemogenesis. Overall, this triple gene system expands our research spectrum in current conditional gene knockout strains and benefits our CML translational research. PMID:27150093

  4. The Mouse Grimace Scale: A Clinically Useful Tool?

    PubMed Central

    Miller, Amy L.; Leach, Matthew C.

    2015-01-01

    Medical research has a heavy and continuing demand for rodent models across a range of disciplines. Behavioural assessment of pain in such models is highly time consuming, thus limiting the number of models and analgesics that can be studied. Facial expressions are widely used to assess pain in human infants. Recently the mouse grimace scale (MGS) has been developed and shown to be accurate and reliable, requiring only a short amount of training for the observer. This system therefore has the potential to become a highly useful tool both in pain research and clinical assessment of mouse pain. To date, the MGS has only been used as a research tool, however there is increasing interest in its use in cage-side clinical assessment. It is often wrongly assumed that MGS scores of animals not in pain (i.e. at baseline) are zero. Here, we aimed to assess the variability in baseline MGS scores between cohorts, sexes and strains of mice. Establishing the presence of a consistent baseline MGS score could lead to a valuable clinical pain assessment tool for mice when baseline information from the individual mouse may not be available as a comparator. Results demonstrated a significant difference in baseline MGS scores between both sexes (males > females) and strains of mice. The method used to score the facial action units (Live vs. retrospectively from still images) demonstrated significant differences in scores with live scores being significantly lower than retrospective scoring from images. The level of variation shown demonstrates the need for further research to be undertaken with regard to establishing baseline MGS scores for specific strains and sexes of mice, taking into account the method of scoring, prior to considering clinical implementation of this method in pain assessment. PMID:26406227

  5. What Are Sprains and Strains?

    MedlinePlus

    ... sprain, one or more ligaments is stretched or torn. What Causes a Sprain? Where Do Sprains Usually ... strain, a muscle or tendon is stretched or torn. What Causes Strains? A strain is caused by ...

  6. Sprains and Strains

    MedlinePlus

    ... people at risk for strains. Gymnastics, tennis, rowing, golf, and other sports that require extensive gripping can ... Trials and You was designed to help people learn more about clinical trials, why they matter, and ...

  7. Nanowires enabling strained photovoltaics

    SciTech Connect

    Greil, J.; Bertagnolli, E.; Lugstein, A.; Birner, S.

    2014-04-21

    Photovoltaic nano-devices have largely been relying on charge separation in conventional p-n junctions. Junction formation via doping, however, imposes major challenges in process control. Here, we report on a concept for photovoltaic energy conversion at the nano scale without the need for intentional doping. Our approach relies on charge carrier separation in inhomogeneously strained germanium nanowires (Ge NWs). This concept utilizes the strain-induced gradient in bandgap along tapered NWs. Experimental data confirms the feasibility of strain-induced charge separation in individual vapor-liquid-solid grown Ge NW devices with an internal quantum efficiency of ∼5%. The charge separation mechanism, though, is not inherently limited to a distinct material. Our work establishes a class of photovoltaic nano-devices with its opto-electronic properties engineered by size, shape, and applied strain.

  8. Devising assisted reproductive technologies for wild-derived strains of mice: 37 strains from five subspecies of Mus musculus.

    PubMed

    Mochida, Keiji; Hasegawa, Ayumi; Otaka, Naoki; Hama, Daiki; Furuya, Takashi; Yamaguchi, Masaki; Ichikawa, Eri; Ijuin, Maiko; Taguma, Kyuichi; Hashimoto, Michiko; Takashima, Rika; Kadota, Masayo; Hiraiwa, Noriko; Mekada, Kazuyuki; Yoshiki, Atsushi; Ogura, Atsuo

    2014-01-01

    Wild-derived mice have long offered invaluable experimental models for mouse genetics because of their high evolutionary divergence from laboratory mice. A number of wild-derived strains are available from the RIKEN BioResource Center (BRC), but they have been maintained as living stocks because of the unavailability of assisted reproductive technology (ART). In this study, we sought to devise ART for 37 wild-derived strains from five subspecies of Mus musculus maintained at the BRC. Superovulation of females was effective (more than 15 oocytes per female) for 34 out of 37 strains by treatment with either equine chorionic gonadotropin or anti-inhibin serum, depending on their genetic background (subspecies). The collected oocytes could be fertilized in vitro at mean rates of 79.0% and 54.6% by the optimized protocol using fresh or frozen-thawed spermatozoa, respectively. They were cryopreserved at the 2-cell stage by vitrification with an ethylene glycol-based solution. In total, 94.6% of cryopreserved embryos survived the vitrification procedure and restored their normal morphology after warming. A conventional embryo transfer protocol could be applied to 25 out of the 35 strains tested. In the remaining 10 strains, live offspring could be obtained by a modified embryo transfer protocol using cyclosporin A treatment and co-transfer of ICR (laboratory mouse strain) embryos. Thus, ART for 37 wild-derived strains was devised successfully and is now routinely used for their preservation and transportation. The information provided here might facilitate broader use and wider distribution of wild-derived mice for biomedical research. PMID:25470728

  9. Toxicological comparison of diverse Cylindrospermopsis raciborskii strains: evidence of liver damage caused by a French C raciborskii strain.

    PubMed

    Bernard, C; Harvey, M; Briand, J F; Biré, R; Krys, S; Fontaine, J J

    2003-06-01

    The freshwater cyanobacterium Cylindrospermopsis raciborskii is known to produce toxic effects in several countries. Acute and chronic exposures to C. raciborskii in Australia have been linked to liver damage (hepatotoxicity) with concomitant effects on the kidneys, adrenal glands, small intestine, lungs, thymus, and heart. The alkaloid cylindrospermopsin, which produces these toxic effects, is thought to be a potent inhibitor of protein synthesis. C. raciborskii strains producing cylindrospermopsin or analogue alkaloids have also been reported in Florida, USA, and Thailand. Brazilian isolates of C. raciborskii are also toxic but act by a different mechanism, causing acute death in mice with neurotoxic symptoms similar to those induced by the saxitoxins. In this article we compare the toxicity in the mouse of a C. raciborskii French strain with C. raciborskii strains from various other sources (Australia, Brazil, Mexico, and Hungary). We tested the toxicity of cell extracts by a mouse bioassay. Acute, fatal neurotoxicity was produced by the Brazilian strain, which was confirmed by liquid chromatography with fluorescence detection of the cell extracts, which revealed the presence of saxitoxin, neosaxitoxin, and decarbamoylsaxitoxin, along with two unidentified compounds. Acute hepatotoxicity with severe liver, kidney, and thymus damage was observed with the Australian cylindrospermopsin-producing strain. The Mexican and Hungarian strains were not found to be toxic to mice in our experimental conditions. No animals died after exposure to the extracts of the French C. raciborskii strain. Histological examination of the liver revealed moderate, multifocal necrosis characterized by small areas of hepatocellular necrosis, combined with disorganization of the parenchyma and congestion of the inner sinusoid. These symptoms and lesions resembled those induced by cylindrospermopsin, but the chemical analysis performed by liquid chromatography coupled with either a diode

  10. A Tetrodotoxin-Producing Vibrio Strain, LM-1, from the Puffer Fish Fugu vermicularis radiatus

    PubMed Central

    Lee, Myoung-Ja; Jeong, Dong-Youn; Kim, Woo-Seong; Kim, Hyun-Dae; Kim, Cheorl-Ho; Park, Won-Whan; Park, Yong-Ha; Kim, Kyung-Sam; Kim, Hyung-Min; Kim, Dong-Soo

    2000-01-01

    Identification of tetrodotoxin (TTX) and its derivatives produced from a Vibrio strain in the intestine of the puffer fish Fugu vermicularis radiatus was performed by thin-layer chromatography, electrophoresis, high-performance liquid chromatography, and gas chromatography-mass spectrometry, together with a mouse bioassay for toxicity. It was demonstrated that the isolated bacterium produced TTX, 4-epi-TTX, and anhTTX during cultivation, suggesting that Vibrio strains are responsible for the toxification of the puffer fish. PMID:10742263

  11. Strain-dependent variations in visceral sensitivity: relationship to stress, anxiety and spinal glutamate transporter expression.

    PubMed

    Moloney, R D; Dinan, T G; Cryan, J F

    2015-04-01

    Responses to painful stimuli differ between populations, ethnic groups, sexes and even among individuals of a family. However, data regarding visceral pain are still lacking. Thus, we investigated differences in visceral nociception across inbred and outbred mouse strains using colorectal distension. Anxiety and depression-like behaviour were assessed using the open field and forced swim test as well as the corticosterone stress response. Possible mechanistic targets [excitatory amino acid transporter (EAAT-1), brain-derived neurotrophic factor (BDNF) and 5HT1A receptor] were also assessed using quantitative real-time polymerase chain reaction. Adult, male, inbred and outbred mouse strains were used in all assays (inbred strains; CBA/J Hsd, C3H/HeNHsd, BALB/c OlaHsd, C57 BL/6JOlaHsd, DBA/2J RccHsd, CAST/EiJ, SM/J, A/J OlaHsd, 129P2/OlaHsd, FVB/NHan Hsd and outbred strains: Swiss Webster, CD-1). mRNA expression levels of EAAT-1, BDNF and 5HT1A receptor (HTR1A) were quantified in the lumbosacral spinal cord, amygdala and hippocampus. A significant effect of strain was found in visceral sensitivity, anxiety and depressive-like behaviours. Strain differences were also seen in both baseline and stress-induced corticosterone levels. CBA/J mice consistently exhibited heightened visceral sensitivity, anxiety behaviour and depression-like behaviour which were associated with decreased spinal EAAT-1 and hippocampal BDNF and HTR1A. Our results show the CBA/J mouse strain as a novel mouse model to unravel the complex mechanisms of brain-gut axis disorders such as irritable bowel syndrome, in particular the underlying mechanisms of visceral hypersensitivity, for which there is great need. Furthermore, this study highlights the importance of genotype and the consequences for future development of transgenic strains in pain research. PMID:25851919

  12. Senescence-accelerated mouse (SAM): a biogerontological resource in aging research.

    PubMed

    Takeda, T

    1999-01-01

    The senescence-accelerated mouse (SAM), consisting of 14 senescence-prone inbred strains (SAMP) and 4 senescence-resistant inbred strains (SAMR) has been under development since 1970 through the selective inbreeding of AKR/J strain mice donated by the Jackson laboratory in 1968, based on the data of the grading score of senescence, life span, and pathologic phenotypes. The characteristic feature of aging common to all SAMP and SAMR mice is accelerated senescence and normal aging, respectively. Furthermore, SAMP and SAMR strains manifest various pathobiological phenotypes which include such neurobiological phenotypes as deficits in learning and memory, emotional disorders, abnormal circadian rhythms, brain atrophy, hearing impairment, etc., and are often characteristic enough to differentiate the strains. Various efforts are currently being made using the SAM model to clarify the underlying mechanisms in accelerated senescence as well as the etiopathogenic mechanisms in age-associated pathobiologies. Genetic background and significance of SAM development are discussed. PMID:10537019

  13. MEMS Graphene Strain Sensor

    NASA Astrophysics Data System (ADS)

    Young, Clinton Wen-Chieh

    Graphene is a two dimensional honeycomb structure of sp2 hybridized carbon atoms that has possibilities in many applications due to its excellent mechanical and electrical properties. One application for Graphene is in the field of sensors. Graphene's electronic properties do not degrade when it undergoes mechanical strain which is advantageous for strain sensors. In this thesis, certain properties, such as the piezo-resistivity and flexibility, of graphene will be explored to show how they can be utilized to make a strain sensing device. Our original fabrication process of patterning graphene and the transfer process of graphene onto a flexible substrate will be discussed. The development of a stretchable and flexible graphene based rosette strain sensor will also be detailed. Developing a novel, reliable patterning process for the graphene is the first step to manufacture a stretchable graphene based sensor. The graphene was patterned using a photolithography and etching process that was developed by our research team, then it was transferred to a flexible polymer substrate with the use of a combination of soft lithography and wet etching of the Ni foil with ferric chloride solution. Graphene patterning is an essential step in fabricating reliable and sensitive sensors. With this process, graphene can be consistently patterned into different shapes and sizes. To utilize the graphene as the sensing material it also needs to be transferred onto a flexible substrate. The innovative transfer process developed by our research team consistently adheres graphene to a flexible PDMS substrate while removing the original nickel substrate. In the end, the graphene was transferred from the metal substrate to the desired flexible substrate. This process was repeated multiple times to create a stack and multilayer device. While many graphene-based strain sensors have been developed, they are uni-directional and can only measure the strain applied on the sensor in a principle

  14. The neuronal nicotinic acetylcholine receptor {alpha}7 subunit gene: Cloning, mapping, structure, and targeting in mouse

    SciTech Connect

    Orr-Urtreger, A.; Baldini, A.; Beaudet, A.L.

    1994-09-01

    The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 subunits, respectively. Using an interspecies backcross panel, the murine gene was mapped to chromosome 7 near the p locus, a region syntenic with human chromosome 15; the human gene (CHRNA7) was confirmed to map to 15q13-q14 by FISH. To generate a mouse {alpha}7 mutant by homologous recombination, we have constructed a replacement vector which will delete transmembrane domains II-IV and the cytoplasmic domain from the gene product. Recombinant embryonic stem (ES) cell clones were selected and used to develop mouse chimeras that are currently being bred to obtain germline transmission.

  15. Genetic Architecture of Insulin Resistance in the Mouse

    PubMed Central

    Parks, Brian W.; Sallam, Tamer; Mehrabian, Margarete; Psychogios, Nikolas; Hui, Simon T.; Norheim, Frode; Castellani, Lawrence W.; Rau, Christoph; Pan, Calvin; Phun, Jennifer; Zhou, Zhenqi; Yang, Wen-Pin; Neuhaus, Isaac; Gargalovic, Peter S.; Kirchgessner, Todd G.; Graham, Mark; Lee, Richard; Tontonoz, Peter; Gerszten, Robert E.; Hevener, Andrea L.; Lusis, Aldons J.

    2015-01-01

    SUMMARY Insulin Resistance (IR) is a complex trait with multiple genetic and environmental components. Confounded by large differences between the sexes, environment and disease pathology, the genetic basis of IR has been difficult to dissect. Here we examine IR and related traits in a diverse population of more than 100 unique male and female inbred mouse strains after feeding a diet rich in fat and refined carbohydrates. Our results show dramatic variation in IR among strains of mice and widespread differences between sexes that is dependent on genotype. We uncover more than 15 genome-wide significant loci and validate a gene, Agpat5, associated with IR. We also integrate plasma metabolite levels and global gene expression from liver and adipose tissue to identify metabolite Quantitative Trait Loci (mQTL) and expression QTL (eQTL), respectively. Our results provide a resource for analysis of interactions between diet, sex and genetic background in IR. PMID:25651185

  16. Neurotropism of Saffold virus in a mouse model.

    PubMed

    Sorgeloos, Frédéric; Lardinois, Cécile; Jacobs, Sophie; van Kuppeveld, Frank J M; Kaspers, Bernd; Michiels, Thomas

    2016-06-01

    Saffold virus (SAFV) is a highly seroprevalent human Cardiovirus discovered recently. No clear association between SAFV infection and human disease has been established. Rare infection cases, however, correlated with neurological symptoms. To gain insight into the pathogenesis potential of the virus, we performed experimental mouse infection with SAFV strains of genotypes 2 and 3 (SAFV-2 and SAFV-3). After intraperitoneal infection, both strains exhibited a typical Cardiovirus tropism. Viral load was most prominent in the pancreas. Heart, spleen, brain and spinal cord were also infected. In IFN-receptor 1 deficient (IFNAR-KO) mice, SAFV-3 caused a severe encephalitis. The virus was detected by immunohistochemistry in many parts of the brain and spinal cord, both in neurons and astrocytes, but astrocyte infection was more extensive. In vitro, SAFV-3 also infected astrocytes better than neurons in mixed primary cultures. Astrocytes were, however, very efficiently protected by IFN-α/β treatment. PMID:26959376

  17. 10. international mouse genome conference

    SciTech Connect

    Meisler, M.H.

    1996-12-31

    Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.

  18. Comparative mRNA analysis of behavioral and genetic mouse models of aggression.

    PubMed

    Malki, Karim; Tosto, Maria G; Pain, Oliver; Sluyter, Frans; Mineur, Yann S; Crusio, Wim E; de Boer, Sietse; Sandnabba, Kenneth N; Kesserwani, Jad; Robinson, Edward; Schalkwyk, Leonard C; Asherson, Philip

    2016-04-01

    Mouse models of aggression have traditionally compared strains, most notably BALB/cJ and C57BL/6. However, these strains were not designed to study aggression despite differences in aggression-related traits and distinct reactivity to stress. This study evaluated expression of genes differentially regulated in a stress (behavioral) mouse model of aggression with those from a recent genetic mouse model aggression. The study used a discovery-replication design using two independent mRNA studies from mouse brain tissue. The discovery study identified strain (BALB/cJ and C57BL/6J) × stress (chronic mild stress or control) interactions. Probe sets differentially regulated in the discovery set were intersected with those uncovered in the replication study, which evaluated differences between high and low aggressive animals from three strains specifically bred to study aggression. Network analysis was conducted on overlapping genes uncovered across both studies. A significant overlap was found with the genetic mouse study sharing 1,916 probe sets with the stress model. Fifty-one probe sets were found to be strongly dysregulated across both studies mapping to 50 known genes. Network analysis revealed two plausible pathways including one centered on the UBC gene hub which encodes ubiquitin, a protein well-known for protein degradation, and another on P38 MAPK. Findings from this study support the stress model of aggression, which showed remarkable molecular overlap with a genetic model. The study uncovered a set of candidate genes including the Erg2 gene, which has previously been implicated in different psychopathologies. The gene networks uncovered points at a Redox pathway as potentially being implicated in aggressive related behaviors. © 2016 Wiley Periodicals, Inc. PMID:26888158

  19. Mouse models of human cancer.

    PubMed

    Böck, Barbara C; Stein, Ulrike; Schmitt, Clemens A; Augustin, Hellmut G

    2014-09-01

    The Helmholtz Alliance Preclinical Comprehensive Cancer Center (PCCC; www.helmholtz-pccc.de) hosted the "1st International Kloster Seeon Meeting on Mouse Models of Human Cancer" in the Seeon monastery (Germany) from March 8 to 11, 2014. The meeting focused on the development and application of novel mouse models in tumor research and high-throughput technologies to overcome one of the most critical bottlenecks in translational bench-to-bedside tumor biology research. Moreover, the participants discussed basic molecular mechanisms underlying tumor initiation, progression, metastasis, and therapy resistance, which are the prerequisite for the development of novel treatment strategies and clinical applications in cancer therapy. PMID:25136075

  20. Dynamics of chromosomal aberrations in male mice of various strains during aging.

    PubMed

    Rozenfel'd, S V; Togo, E F; Mikheev, V S; Popovich, I G; Zabezhinskii, M A; Anisimov, V N

    2001-05-01

    We studied the incidence of chromosome aberrations in bone marrow cells and primary spermatocytes in various mouse strains. Experiments were performed on SAMP mice (accelerated aging), control SAMR mice, and long-living CBA and SHR mice. Experiments revealed a positive correlation between the age and the incidence of mutations in their somatic cells and gametes. PMID:11550060

  1. Comparison of activity to stimulate mucosal IgA production between Leuconostoc mesenteroides strain NTM048 and type strain JCM6124 in mice

    PubMed Central

    MATSUZAKI, Chiaki; MATSUMOTO, Kenji; KATOH, Toshihiko; YAMAMOTO, Kenji; HISA, Keiko

    2015-01-01

    The effects of Leuconostoc mesenteroides strain NTM048 and type strain JCM6124T on the murine immune system were characterized. Although the bacterial cells and exopolysaccharides of each strain induced immunoglobulin A production in Peyer’s patch cells, the effects of NTM048 were more potent than those of JCM6124T. Oral administration of the cells of each strain increased the fecal immunoglobulin A content in NTM048-treated mice, but not in JCM6124T-treated mice. A flow cytometric analysis showed that the CD4+ T-cell populations in the mouse spleens tended to increase in the NTM048 group. These results suggest that immunomodulating ability is characteristic of strain NTM048. PMID:26858930

  2. The atomic strain tensor

    SciTech Connect

    Mott, P.H.; Argon, A.S. ); Suter, U.W. Massachusetts Institute of Technology, Cambridge, MA )

    1992-07-01

    A definition of the local atomic strain increments in three dimensions and an algorithm for computing them is presented. An arbitrary arrangement of atoms is tessellated in to Delaunay tetrahedra, identifying interstices, and Voronoi polyhedra, identifying atomic domains. The deformation gradient increment tensor for interstitial space is obtained from the displacement increments of the corner atoms of Delaunay tetrahedra. The atomic site strain increment tensor is then obtained by finding the intersection of the Delaunay tetrahedra with the Voronoi polyhedra, accumulating the individual deformation gradient contributions of the intersected Delaunay tetrahedra into the Voronoi polyhedra. An example application is discussed, showing how the atomic strain clarifies the relative local atomic movement for a polymeric glass treated at the atomic level. 6 refs. 10 figs.

  3. Strain gauge installation tool

    DOEpatents

    Conard, L.M.

    1998-06-16

    A tool and a method are disclosed for attaching a strain gauge to a test specimen by maintaining alignment of, and applying pressure to, the strain gauge during the bonding of the gauge to the specimen. The tool comprises rigid and compliant pads attached to a spring-loaded clamp. The pads are shaped to conform to the specimen surface to which the gauge is to be bonded. The shape of the pads permits the tool to align itself to the specimen and to maintain alignment of the gauge to the specimen during the bond curing process. A simplified method of attaching a strain gauge is provided by use of the tool. 6 figs.

  4. Diffusion on strained surfaces

    NASA Astrophysics Data System (ADS)

    Schroeder, M.; Wolf, D. E.

    1997-03-01

    The change of diffusion kinetics when elastic fields are present is discussed for diffusion on (001) surfaces of simple cubic, fcc and bcc lattices. All particles interact pairwise with a Lennard-Jones potential. The simple cubic lattice was stabilized by an anisotropic prefactor. It is found that generically compressive strain enhances diffusion whereas tensile strain increases the activation barrier. An approximately linear dependence of the barrier in a wide range of misfits is found. In heteroepitaxy, diffusion on top of large clusters is inhomogeneous and anisotropic. The kinetics close to edges and centers of islands are remarkably different. In many cases changes of binding energies are small compared to those of saddle point energies. Thermodynamic arguments (minimization of free energy) are not appropriate to describe diffusion on strained surfaces in these cases.

  5. Annihilation of strained vortices

    NASA Astrophysics Data System (ADS)

    Kimura, Yoshifumi

    2014-11-01

    As an initial stage of vortex reconnection, approach of nearly anti-parallel vortices has often been observed experimentally and studied numerically. Inspired by the recent experiment by Kleckner and Irvine on the dynamics of knotted vortices, we have studied the motion of two anti-parellel Burgers vortices driven by an axisymmetric linear straining field. We first extend the Burgers vortex solution which is a steady exact solution of the Navier-Stokes equation to a time-dependent exact solution. Then by superposing two such solutions, we investigate the annihilation process analytically. We can demonstrate that during the annihilation process the total vorticity decays exponentially on a time-scale proportional to the inverse of the rate of strain, even as the kinematic viscosity tends to 0. The analytic results are compared with the numerical simulations of two strained vortices with the vortex-vortex nonlinear interaction by Buntine and Pullin.

  6. Strain isolated ceramic coatings

    NASA Technical Reports Server (NTRS)

    Tolokan, R. P.; Brady, J. B.; Jarrabet, G. P.

    1985-01-01

    Plasma sprayed ceramic coatings are used in gas turbine engines to improve component temperature capability and cooling air efficiency. A compliant metal fiber strain isolator between a plasma sprayed ceramic coating and a metal substrate improves ceramic durability while allowing thicker coatings for better insulation. Development of strain isolated coatings has concentrated on design and fabrication of coatings and coating evaluation via thermal shock testing. In thermal shock testing, five types of failure are possible: buckling failure im compression on heat up, bimetal type failure, isothermal expansion mismatch failure, mudflat cracking during cool down, and long term fatigue. A primary failure mode for thermally cycled coatings is designated bimetal type failure. Bimetal failure is tensile failure in the ceramic near the ceramic-metal interface. One of the significant benefits of the strain isolator is an insulating layer protecting the metal substrate from heat deformation and thereby preventing bimetal type failure.

  7. International Mouse Phenotyping Consortium (IMPC) —

    Cancer.gov

    The International Mouse Phenotyping Consortium (IMPC) comprises a group of major mouse genetics research institutions along with national funding organisations formed to address the challenge of developing an encyclopedia of mammalian gene function.

  8. Predominant contribution of cis-regulatory divergence in the evolution of mouse alternative splicing

    PubMed Central

    Gao, Qingsong; Sun, Wei; Ballegeer, Marlies; Libert, Claude; Chen, Wei

    2015-01-01

    Divergence of alternative splicing represents one of the major driving forces to shape phenotypic diversity during evolution. However, the extent to which these divergences could be explained by the evolving cis-regulatory versus trans-acting factors remains unresolved. To globally investigate the relative contributions of the two factors for the first time in mammals, we measured splicing difference between C57BL/6J and SPRET/EiJ mouse strains and allele-specific splicing pattern in their F1 hybrid. Out of 11,818 alternative splicing events expressed in the cultured fibroblast cells, we identified 796 with significant difference between the parental strains. After integrating allele-specific data from F1 hybrid, we demonstrated that these events could be predominately attributed to cis-regulatory variants, including those residing at and beyond canonical splicing sites. Contrary to previous observations in Drosophila, such predominant contribution was consistently observed across different types of alternative splicing. Further analysis of liver tissues from the same mouse strains and reanalysis of published datasets on other strains showed similar trends, implying in general the predominant contribution of cis-regulatory changes in the evolution of mouse alternative splicing. PMID:26134616

  9. Female Presence and Estrous State Influence Mouse Ultrasonic Courtship Vocalizations

    PubMed Central

    Hanson, Jessica L.; Hurley, Laura M.

    2012-01-01

    The laboratory mouse is an emerging model for context-dependent vocal signaling and reception. Mouse ultrasonic vocalizations are robustly produced in social contexts. In adults, male vocalization during courtship has become a model of interest for signal-receiver interactions. These vocalizations can be grouped into syllable types that are consistently produced by different subspecies and strains of mice. Vocalizations are unique to individuals, vary across development, and depend on social housing conditions. The behavioral significance of different syllable types, including the contexts in which different vocalizations are made and the responses listeners have to different types of vocalizations, is not well understood. We examined the effect of female presence and estrous state on male vocalizations by exploring the use of syllable types and the parameters of syllables during courtship. We also explored correlations between vocalizations and other behaviors. These experimental manipulations produced four main findings: 1) vocalizations varied among males, 2) the production of USVs and an increase in the use of a specific syllable type were temporally related to mounting behavior, 3) the frequency (kHz), bandwidth, and duration of syllables produced by males were influenced by the estrous phase of female partners, and 4) syllable types changed when females were removed. These findings show that mouse ultrasonic courtship vocalizations are sensitive to changes in female phase and presence, further demonstrating the context-sensitivity of these calls. PMID:22815817

  10. The mouse Gene Expression Database (GXD): 2011 update

    PubMed Central

    Finger, Jacqueline H.; Smith, Constance M.; Hayamizu, Terry F.; McCright, Ingeborg J.; Eppig, Janan T.; Kadin, James A.; Richardson, Joel E.; Ringwald, Martin

    2011-01-01

    The Gene Expression Database (GXD) is a community resource of mouse developmental expression information. GXD integrates different types of expression data at the transcript and protein level and captures expression information from many different mouse strains and mutants. GXD places these data in the larger biological context through integration with other Mouse Genome Informatics (MGI) resources and interconnections with many other databases. Web-based query forms support simple or complex searches that take advantage of all these integrated data. The data in GXD are obtained from the literature, from individual laboratories, and from large-scale data providers. All data are annotated and reviewed by GXD curators. Since the last report, the GXD data content has increased significantly, the interface and data displays have been improved, new querying capabilities were implemented, and links to other expression resources were added. GXD is available through the MGI web site (www.informatics.jax.org), or directly at www.informatics.jax.org/expression.shtml. PMID:21062809

  11. Toxicokinetics and toxicodynamics of paraquat accumulation in mouse brain

    PubMed Central

    Prasad, Kavita; Tarasewicz, Elizabeth; Mathew, Jason; Ohman Strickland, Pamela A.; Buckley, Brian; Richardson, Jason R.; Richfield, Eric K.

    2014-01-01

    Paraquat (PQ) is a potential human neurotoxicant and is used in models of oxidative stress. We determined the toxicokinetics (TK) and toxicodynamics (TD) of PQ in adult mouse brain following repeated or prolonged PQ exposure. PQ accumulated in different brain regions and reached a plateau after ~18 i.p. (10 mg/kg) doses and resulted in modest morbidity and mortality unpredictably associated with dose interval and number. PQ had divergent effects on horizontal locomotor behavior depending on the number of doses. PQ decreased striatal dopamine levels after the 18th to 36th i.p. dose (10 mg/kg) and reduced the striatal level of tyrosine hydroxylase. Drinking water exposure to PQ (0.03– 0.05 mg/ml) did not result in any mortality and resulted in concentration and time dependent levels in the brain. The brain half-life of PQ varied with mouse strain. PQ accumulates and may saturate a site in mouse brain resulting in complex PQ level and duration-related consequences. These findings should alter our risk assessment of this compound and demonstrate a useful, but complex dynamic model for understanding the consequences of PQ in the brain. PMID:19084006

  12. The Mouse Universal Genotyping Array: From Substrains to Subspecies.

    PubMed

    Morgan, Andrew P; Fu, Chen-Ping; Kao, Chia-Yu; Welsh, Catherine E; Didion, John P; Yadgary, Liran; Hyacinth, Leeanna; Ferris, Martin T; Bell, Timothy A; Miller, Darla R; Giusti-Rodriguez, Paola; Nonneman, Randal J; Cook, Kevin D; Whitmire, Jason K; Gralinski, Lisa E; Keller, Mark; Attie, Alan D; Churchill, Gary A; Petkov, Petko; Sullivan, Patrick F; Brennan, Jennifer R; McMillan, Leonard; Pardo-Manuel de Villena, Fernando

    2015-01-01

    Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the genetic integrity of laboratory stocks. We have developed the third generation of the Mouse Universal Genotyping Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array for the house mouse (Mus musculus). The bulk of the content of GigaMUGA is optimized for genetic mapping in the Collaborative Cross and Diversity Outbred populations, and for substrain-level identification of laboratory mice. In addition to 141,090 single nucleotide polymorphism probes, GigaMUGA contains 2006 probes for copy number concentrated in structurally polymorphic regions of the mouse genome. The performance of the array is characterized in a set of 500 high-quality reference samples spanning laboratory inbred strains, recombinant inbred lines, outbred stocks, and wild-caught mice. GigaMUGA is highly informative across a wide range of genetically diverse samples, from laboratory substrains to other Mus species. In addition to describing the content and performance of the array, we provide detailed probe-level annotation and recommendations for quality control. PMID:26684931

  13. The Mouse Universal Genotyping Array: From Substrains to Subspecies

    PubMed Central

    Morgan, Andrew P.; Fu, Chen-Ping; Kao, Chia-Yu; Welsh, Catherine E.; Didion, John P.; Yadgary, Liran; Hyacinth, Leeanna; Ferris, Martin T.; Bell, Timothy A.; Miller, Darla R.; Giusti-Rodriguez, Paola; Nonneman, Randal J.; Cook, Kevin D.; Whitmire, Jason K.; Gralinski, Lisa E.; Keller, Mark; Attie, Alan D.; Churchill, Gary A.; Petkov, Petko; Sullivan, Patrick F.; Brennan, Jennifer R.; McMillan, Leonard; Pardo-Manuel de Villena, Fernando

    2015-01-01

    Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the genetic integrity of laboratory stocks. We have developed the third generation of the Mouse Universal Genotyping Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array for the house mouse (Mus musculus). The bulk of the content of GigaMUGA is optimized for genetic mapping in the Collaborative Cross and Diversity Outbred populations, and for substrain-level identification of laboratory mice. In addition to 141,090 single nucleotide polymorphism probes, GigaMUGA contains 2006 probes for copy number concentrated in structurally polymorphic regions of the mouse genome. The performance of the array is characterized in a set of 500 high-quality reference samples spanning laboratory inbred strains, recombinant inbred lines, outbred stocks, and wild-caught mice. GigaMUGA is highly informative across a wide range of genetically diverse samples, from laboratory substrains to other Mus species. In addition to describing the content and performance of the array, we provide detailed probe-level annotation and recommendations for quality control. PMID:26684931

  14. Nonspecific airway reactivity in a mouse model of asthma

    SciTech Connect

    Collie, D.D.; Wilder, J.A.; Bice, D.E.

    1995-12-01

    Animal models are indispensable for studies requiring an intact immune system, especially for studying the pathogenic mechanisms in atopic diseases, regulation of IgE production, and related biologic effects. Mice are particularly suitable and have been used extensively for such studies because their immune system is well characterized. Further, large numbers of mutants or inbred strains of mice are available that express deficiencies of individual immunologic processes, inflammatory cells, or mediator systems. By comparing reactions in such mice with appropriate control animals, the unique roles of individual cells or mediators may be characterized more precisely in the pathogenesis of atopic respiratory diseases including asthma. However, given that asthma in humans is characterized by the presence of airway hyperresponsiveness to specific and nonspecific stimuli, it is important that animal models of this disease exhibit similar physiologic abnormalities. In the past, the size of the mouse has limited its versatility in this regard. However, recent studies indicate the feasibility of measuring pulmonary responses in living mice, thus facilitating the physiologic evaluation of putative mouse models of human asthma that have been well charcterized at the immunologic and patholigic level. Future work will provide details of the morphometry of the methacholine-induced bronchoconstriction and will further seek to determine the relationship between cigarette smoke exposure and the development of NS-AHR in the transgenic mouse model.

  15. Congenic mapping and candidate sequencing of susceptibility genes for Type 1 diabetes in the NOD mouse.

    PubMed

    Ikegami, Hiroshi; Fujisawa, Tomomi; Makino, Susumu; Ogihara, Toshio

    2003-11-01

    Inheritance of type 1 diabetes is polygenic with a major susceptibility gene located in the major histocompatibility complex (MHC). In addition to MHC-linked susceptibility, a number of susceptibility genes have been mapped outside the MHC in both humans and animal models. In order to localize and identify susceptibility genes for type 1 diabetes, we have developed a series of congenic strains in which either susceptibility intervals from the NOD mouse, a mouse model of type 1 diabetes, were introgressed onto control background genes or protective intervals from control strains were introgressed onto NOD background genes. NOD. CTS-H-2 congenic mice, which possess recombinant MHC with NOD alleles at class II A and E genes, which are candidates for Idd1, revealed that Idd1 consists of multiple components, one in class II (Idd1) and the other adjacent to, but distinct from, Idd1 (Idd16). Phenotypes of NOD. IIS-Idd3 congenic mice, which share the same alleles at both Il2 and Il21 as the NOD mouse, were indistinguishable from the NOD parental strain, indicating that both Il2 and Il21 are candidates for Idd3. In contrast, NOD. IIS-Idd10 congenic mice, which share the same alleles at Fcgr1, a previous candidate for Idd10, as the NOD mouse, were protected from type 1 diabetes, suggesting that Fcgr1 may not be responsible for the Idd10 effect. These data suggest that the use of strain colony closely related to a disease model to find the same candidate mutation on different haplotypes and make congenic strains with this recombinant chromosome, termed ancestral haplotype congenic mapping, is an effective strategy for fine mapping and identification of genes responsible for complex traits. PMID:14679059

  16. Biochemical and Functional Comparisons of mdx and Sgcg−/− Muscular Dystrophy Mouse Models

    PubMed Central

    Roberts, Nathan W.; Holley-Cuthrell, Jenan; Gonzalez-Vega, Magdalis; Mull, Aaron J.; Heydemann, Ahlke

    2015-01-01

    Mouse models have provided an essential platform to investigate facets of human diseases, from etiology, diagnosis, and prognosis, to potential treatments. Muscular dystrophy (MD) is the most common human genetic disease occurring in approximately 1 in 2500 births. The mdx mouse, which is dystrophin-deficient, has long been used to model this disease. However, this mouse strain displays a rather mild disease course compared to human patients. The mdx mice have been bred to additional genetically engineered mice to worsen the disease. Alternatively, other genes which cause human MD have been genetically disrupted in mice. We are now comparing disease progression from one of these alternative gene disruptions, the γ-sarcoglycan null mouse Sgcg−/− on the DBA2/J background, to the mdx mouse line. This paper aims to assess the time-course severity of the disease in the mouse models and determine which is best for MD research. The Sgcg−/− mice have a more severe phenotype than the mdx mice. Muscle function was assessed by plethysmography and echocardiography. Histologically the Sgcg−/− mice displayed increased fibrosis and variable fiber size. By quantitative Evan's blue dye uptake and hydroxyproline content two key disease determinants, membrane permeability and fibrosis respectively, were also proven worse in the Sgcg−/− mice. PMID:26064876

  17. Local Strain Evaluation of Strained-SOI Structures

    NASA Astrophysics Data System (ADS)

    Usuda, Koji; Mizuno, Tomohisa; Numata, Toshinori; Tezuka, Tsutomu; Sugiyama, Naoharu; Moriyama, Yoshihiko; Nakaharai, Shu; Takagi, Shin-Ichi

    The strain relaxation within a strained-Si on SiGe on insulator (SGOI) structure might be one of the key issues in development of strained-Si MOSFET devices for high-performance ULSIs. In order to investigate the strain relaxation within the thin strained-Si layers, a new characterization technique to directly evaluate a local strain variation in the layers is required. Hence, we have developed the nano-beam electron diffraction (NBD) method which has a lateral resolution of 10 nm and a strain resolution of 0.1%. In this paper, we discuss a detailed investigation of whether the NBD method could be utilized to clarify a strain in a strained-Si layer on the SGOI structures.

  18. ConStrains identifies microbial strains in metagenomic datasets

    PubMed Central

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-01-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived data sets provides insights into microbial community dynamics. PMID:26344404

  19. ConStrains identifies microbial strains in metagenomic datasets.

    PubMed

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-10-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived datasets provides insights into microbial community dynamics. PMID:26344404

  20. Mouse models for radiation-induced cancers.

    PubMed

    Rivina, Leena; Davoren, Michael J; Schiestl, Robert H

    2016-09-01

    Potential ionising radiation exposure scenarios are varied, but all bring risks beyond the simple issues of short-term survival. Whether accidentally exposed to a single, whole-body dose in an act of terrorism or purposefully exposed to fractionated doses as part of a therapeutic regimen, radiation exposure carries the consequence of elevated cancer risk. The long-term impact of both intentional and unintentional exposure could potentially be mitigated by treatments specifically developed to limit the mutations and precancerous replication that ensue in the wake of irradiation The development of such agents would undoubtedly require a substantial degree of in vitro testing, but in order to accurately recapitulate the complex process of radiation-induced carcinogenesis, well-understood animal models are necessary. Inbred strains of the laboratory mouse, Mus musculus, present the most logical choice due to the high number of molecular and physiological similarities they share with humans. Their small size, high rate of breeding and fully sequenced genome further increase its value for use in cancer research. This chapter will review relevant m. musculus inbred and F1 hybrid animals of radiation-induced myeloid leukemia, thymic lymphoma, breast and lung cancers. Method of cancer induction and associated molecular pathologies will also be described for each model. PMID:27209205

  1. Mouse infection models for space flight immunology

    NASA Technical Reports Server (NTRS)

    Chapes, Stephen Keith; Ganta, Roman Reddy; Chapers, S. K. (Principal Investigator)

    2005-01-01

    Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.

  2. Third harmonic generation microscopy of a mouse retina

    PubMed Central

    Lei, Tim C.; Domingue, Scott R.; Kahook, Malik Y.; Bartels, Randy A.; Ammar, David A.

    2015-01-01

    Purpose To demonstrate lipid-specific imaging of the retina through the use of third harmonic generation (THG), a multiphoton microscopic technique in which tissue contrast is generated from optical inhomogeneities. Methods A custom fiber laser and multiphoton microscope was constructed and optimized for simultaneous two-photon autofluorescence (TPAF) and THG retinal imaging. Imaging was performed using fixed-frozen sections of mouse eyes without the use of exogenous fluorescent dyes. In parallel experiments, a fluorescent nuclear stain was used to verify the location of the retinal cell nuclei. Results Simultaneous THG and TPAF images revealed all retinal layers with subcellular resolution. In BALB/c strains, the THG signal stems from the lipidic organelles of the cellular and nuclear membranes. In the C57BL/6 strain, the THG signal from the RPE cells originates from the pigmented granules. Conclusions THG microscopy can be used to image structures of the mouse retina using contrast inherent to the tissue and without the use of a fluorescent dye or exogenously expressed recombinant protein. PMID:25999681

  3. The NOD mouse as a model of SLE.

    PubMed

    Silveira, P A; Baxter, A G

    2001-01-01

    In addition to developing a high incidence of type 1 diabetes caused by a specific autoimmune response against pancreatic beta cells in the islets of Langerhans, NOD mice also demonstrate spontaneous autoimmunity to other targets including the thymus, adrenal gland, salivary glands, thyroid, testis, nuclear components and red blood cells. Moreover, treatment of pre-diabetic NOD mice with an intravenous dose of heat killed Mycobacterium bovis (M. bovis; bacillus Calmette-Guèrin (BCG)) protects them from developing type 1 diabetes, but instead precipitates an autoimmune rheumatic disease similar to systemic lupus erythematosus (SLE), characterised by accelerated and increased incidence of haemolytic anaemia (HA), anti-nuclear autoantibody (ANA) production, exacerbation of sialadenitis, and the appearance of immune complex-mediated glomerulonephritis (GN). The reciprocal switching between the two phenotypes by a single environmental trigger (mycobacterial exposure) raised the possibility that genetic susceptibility for type 1 diabetes and SLE may be conferred by a single collection of genes in the NOD mouse. This review will focus on the genetic components predisposing NOD mice to SLE induced by BCG treatment and compare them to previously determined diabetes susceptibility genes in this strain and SLE susceptibility genes in the BXSB, MRL and the New Zealand mouse strains. PMID:11681493

  4. Lipid Extraction from Mouse Feces

    PubMed Central

    Kraus, Daniel; Yang, Qin; Kahn, Barbara B.

    2016-01-01

    The analysis of feces composition is important for the study of energy metabolism, which comprises various measurements of energy intake, energy expenditure, and energy wasting. The current protocol describes how to measure energy-dense lipids in mouse feces using a modification of the method proposed by Folch et al. (1957). PMID:27110587

  5. Rat spermatogenesis in mouse testis

    PubMed Central

    Clouthier, David E.; Avarbock, Mary R.; Maika, Shanna D.; Hammer, Robert E.

    2016-01-01

    Recently, transplantation of mouse donor spermatogonial stem cells from a fertile testis to an infertile recipient mouse testis was described1,2. The donor cells established spermatogenesis in the seminiferous tubules of the host, and normal spermatozoa were produced. In the most successful transplants, the recipient mice were fertile and sired up to 80 per cent of progeny from donor cells2. Here we examine the feasibility of transplanting spermatogonial stem cells from other species to the mouse seminiferous tubule to generate spermatogenesis. Marked testis cells from transgenic rats were transplanted to the testes of immunodeficient mice, and in all of 10 recipient mice (in 19 of 20 testes), rat spermatogenesis occurred. Epididymides of eight mice were examined, and the three from mice with the longest transplants (≥110 days) contained rat spermatozoa with normal morphology. The generation of rat spermatogenesis in mouse testes suggests that spermatogonial stem cells of many species could be transplanted, and opens the possibility of xenogeneic spermatogenesis for other species. PMID:8632797

  6. Mouse models of myasthenia gravis.

    PubMed

    Ban, Joanne; Phillips, William D

    2015-01-01

    Myasthenia gravis is a muscle weakness disease characterized by autoantibodies that target components of the neuromuscular junction, impairing synaptic transmission. The most common form of myasthenia gravis involves antibodies that bind the nicotinic acetylcholine receptors in the postsynaptic membrane. Many of the remaining cases are due to antibodies against muscle specific tyrosine kinase (MuSK). Recently, autoantibodies against LRP4 (another component of the MuSK signaling complex in the postsynaptic membrane) were identified as the likely cause of myasthenia gravis in some patients. Fatiguing weakness is the common symptom in all forms of myasthenia gravis, but muscles of the body are differentially affected, for reasons that are not fully understood. Much of what we have learnt about the immunological and neurobiological aspects of the pathogenesis derives from mouse models. The most widely used mouse models involve either passive transfer of autoantibodies, or active immunization of the mouse with acetylcholine receptors or MuSK protein. These models can provide a robust replication of many of the features of the human disease. Depending upon the protocol, acute fatiguing weakness develops 2 - 14 days after the start of autoantibody injections (passive transfer) or might require repeated immunizations over several weeks (active models). Here we review mouse models of myasthenia gravis, including what they have contributed to current understanding of the pathogenic mechanisms and their current application to the testing of therapeutics. PMID:25777761

  7. Mouse Models of Rheumatoid Arthritis.

    PubMed

    Caplazi, P; Baca, M; Barck, K; Carano, R A D; DeVoss, J; Lee, W P; Bolon, B; Diehl, L

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients. PMID:26063174

  8. Mouse Cochlear Whole Mount Immunofluorescence

    PubMed Central

    Akil, Omar; Lustig, Lawrence R.

    2016-01-01

    This protocol comprises the entire process of immunofluorescence staining on mouse cochlea whole mount, starting from tissue preparation to the mounting of the tissue. This technique provides “three-dimensional” views of the stained components in order to determine the localization of a protein of interest in the tissue in its natural state and environment. PMID:27547786

  9. APOPTOSIS IN WHOLE MOUSE OVARIES

    EPA Science Inventory

    Apoptosis in Whole Mouse Ovaries
    Robert M. Zucker Susan C. Jeffay and Sally D. Perreault
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711.

  10. Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression

    PubMed Central

    Xiong, Hao; Morrison, Juliet; Ferris, Martin T.; Gralinski, Lisa E.; Whitmore, Alan C.; Green, Richard; Thomas, Matthew J.; Tisoncik-Go, Jennifer; Schroth, Gary P.; Pardo-Manuel de Villena, Fernando; Baric, Ralph S.; Heise, Mark T.; Peng, Xinxia; Katze, Michael G.

    2014-01-01

    Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection. PMID:24902603