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Sample records for a33 antigen-deficient mice

  1. CF750-A33scFv-Fc-Based Optical Imaging of Subcutaneous and Orthotopic Xenografts of GPA33-Positive Colorectal Cancer in Mice

    PubMed Central

    Wei, Danfeng; Fan, Qing; Cai, Huawei; Yang, Hao; Wan, Lin; Li, Lin; Lu, Xiaofeng

    2015-01-01

    Antibody-based imaging agents are attractive as adjuvant diagnostic tools for solid tumors. GPA33 is highly expressed in most human colorectal cancers and has been verified as a diagnostic and therapeutic target. Here, we built an A33scFv-Fc antibody against GPA33 by fusing A33scFv to the Fc fragment of human IgG1 antibodies. The A33scFv-Fc specifically binds GPA33-positive colorectal cancer cells and tumor tissues. After the intravenous injection of mice bearing subcutaneous GPA33-positive LS174T tumor grafts with near-infrared fluorescence probe CF750-labeled A33scFv-Fc (CF750-A33scFv-Fc), high contrast images of the tumor grafts could be kinetically documented within 24?h using an optical imaging system. However, GPA33-negative SMMC7721 tumor grafts could not be visualized by injecting the same amount of CF750-A33scFv-Fc. Moreover, in subcutaneous LS174T tumor-bearing mice, tissue scanning revealed that the CF750-A33scFv-Fc accumulated in the tumor grafts, other than the kidney and liver. In mice with orthotopic tumor transplantations, excrescent LS174T tumor tissues in the colon were successfully removed under guidance by CF750-A33scFv-Fc-based optical imaging. These results indicate that CF750-A33scFv-Fc can target GPA33, suggesting the potential of CF750-A33scFv-Fc as an imaging agent for the diagnosis of colorectal cancer. PMID:26090413

  2. Active vaccination with vaccinia virus A33 protects mice against lethal vaccinia and ectromelia viruses but not against cowpoxvirus; elucidation of the specific adaptive immune response.

    PubMed

    Paran, Nir; Lustig, Shlomo; Zvi, Anat; Erez, Noam; Israely, Tomer; Melamed, Sharon; Politi, Boaz; Ben-Nathan, David; Schneider, Paula; Lachmi, Batel; Israeli, Ofir; Stein, Dana; Levin, Reuven; Olshevsky, Udy

    2013-01-01

    Vaccinia virus protein A33 (A33VACV) plays an important role in protection against orthopoxviruses, and hence is included in experimental multi-subunit smallpox vaccines. In this study we show that single-dose vaccination with recombinant Sindbis virus expressing A33VACV, is sufficient to protect mice against lethal challenge with vaccinia virus WR (VACV-WR) and ectromelia virus (ECTV) but not against cowpox virus (CPXV), a closely related orthopoxvirus. Moreover, a subunit vaccine based on the cowpox virus A33 ortholog (A33CPXV) failed to protect against cowpox and only partially protected mice against VACV-WR challenge. We mapped regions of sequence variation between A33VACV and A33CPXVand analyzed the role of such variations in protection. We identified a single protective region located between residues 104-120 that harbors a putative H-2Kd T cell epitope as well as a B cell epitope - a target for the neutralizing antibody MAb-1G10 that blocks spreading of extracellular virions. Both epitopes in A33CPXV are mutated and predicted to be non-functional. Whereas vaccination with A33VACV did not induce in-vivo CTL activity to the predicted epitope, inhibition of virus spread in-vitro, and protection from lethal VACV challenge pointed to the B cell epitope highlighting the critical role of residue L118 and of adjacent compensatory residues in protection. This epitope's critical role in protection, as well as its modifications within the orthopoxvirus genus should be taken in context with the failure of A33 to protect against CPXV as demonstrated here. These findings should be considered when developing new subunit vaccines and monoclonal antibody based therapeutics against orthopoxviruses, especially variola virus, the etiologic agent of smallpox. PMID:23842430

  3. O-antigen-deficient Francisella tularensis Live Vaccine Strain mutants are ingested via an aberrant form of looping phagocytosis and show altered kinetics of intracellular trafficking in human macrophages.

    PubMed

    Clemens, Daniel L; Lee, Bai-Yu; Horwitz, Marcus A

    2012-03-01

    We examined the uptake and intracellular trafficking of F. tularensis Live Vaccine Strain (LVS) and LVS with disruptions of wbtDEF and wbtI genes essential for synthesis of the O antigen of lipopolysaccharide. Unlike parental bacteria, O-antigen-deficient LVS is efficiently killed by serum with intact complement but not by serum lacking terminal complement components. Opsonization of O-antigen-deficient LVS in serum lacking terminal complement components allows efficient uptake of these live bacteria by macrophages. In the presence of complement, whereas parental F. tularensis LVS is internalized within spacious pseudopod loops, mutant LVS is internalized within tightly juxtaposed multiple onion-like layers of pseudopodia. Without complement, both parental and mutant LVSs are internalized within spacious pseudopod loops. Thus, molecules other than O antigen are important in triggering dramatic pseudopod extensions and uptake by spacious pseudopod loops. Following uptake, both parental and mutant LVSs enter compartments that show limited staining for the lysosomal membrane glycoprotein CD63 and little fusion with secondary lysosomes. Subsequently, both parental and mutant LVSs lose their CD63 staining. Whereas the majority of parental LVS escapes into the cytosol by 6 h after uptake, mutant LVS shows a marked lag but does escape by 1 day after uptake. Despite the altered kinetics of phagosome escape, both mutant and parental strains grow to high levels within human macrophages. Thus, the O antigen plays a role in the morphology of uptake in the presence of complement and the kinetics of intracellular growth but is not essential for escape, survival, altered membrane trafficking, or intramacrophage growth. PMID:22202123

  4. 42 CFR 136a.33 - Grace period.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Grace period. 136a.33 Section 136a.33 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH Transition Provisions § 136a.33 Grace period. (a) Upon...

  5. 42 CFR 136a.33 - Grace period.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Grace period. 136a.33 Section 136a.33 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH Transition Provisions § 136a.33 Grace period. (a) Upon...

  6. Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer

    PubMed Central

    Matho, Michael H.; Schlossman, Andrew; Meng, Xiangzhi; Benhnia, Mohammed Rafii-El-Idrissi; Kaever, Thomas; Buller, Mark; Doronin, Konstantin; Parker, Scott; Peters, Bjoern; Crotty, Shane; Xiang, Yan; Zajonc, Dirk M.

    2015-01-01

    Vaccinia virus A33 is an extracellular enveloped virus (EEV)-specific type II membrane glycoprotein that is essential for efficient EEV formation and long-range viral spread within the host. A33 is a target for neutralizing antibody responses against EEV. In this study, we produced seven murine anti-A33 monoclonal antibodies (MAbs) by immunizing mice with live VACV, followed by boosting with the soluble A33 homodimeric ectodomain. Five A33 specific MAbs were capable of neutralizing EEV in the presence of complement. All MAbs bind to conformational epitopes on A33 but not to linear peptides. To identify the epitopes, we have adetermined the crystal structures of three representative neutralizing MAbs in complex with A33. We have further determined the binding kinetics for each of the three antibodies to wild-type A33, as well as to engineered A33 that contained single alanine substitutions within the epitopes of the three crystallized antibodies. While the Fab of both MAbs A2C7 and A20G2 binds to a single A33 subunit, the Fab from MAb A27D7 binds to both A33 subunits simultaneously. A27D7 binding is resistant to single alanine substitutions within the A33 epitope. A27D7 also demonstrated high-affinity binding with recombinant A33 protein that mimics other orthopoxvirus strains in the A27D7 epitope, such as ectromelia, monkeypox, and cowpox virus, suggesting that A27D7 is a potent cross-neutralizer. Finally, we confirmed that A27D7 protects mice against a lethal challenge with ectromelia virus. PMID:26325270

  7. 8 CFR 245a.33 - Filing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ACT LIFE Act Amendments Family Unity Provisions 245a.33 Filing. (a) General. An application for Family Unity benefits under section 1504 of the LIFE Act Amendments must be filed on a Form I-817... application for Family Unity benefits under the LIFE Act Amendments. The Director will provide the...

  8. 8 CFR 245a.33 - Filing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... NATIONALITY ACT LIFE Act Amendments Family Unity Provisions 245a.33 Filing. (a) General. An application for Family Unity benefits under section 1504 of the LIFE Act Amendments must be filed on a Form I-817... application for Family Unity benefits under the LIFE Act Amendments. The Director will provide the...

  9. 8 CFR 245a.33 - Filing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... NATIONALITY ACT LIFE Act Amendments Family Unity Provisions 245a.33 Filing. (a) General. An application for Family Unity benefits under section 1504 of the LIFE Act Amendments must be filed on a Form I-817... application for Family Unity benefits under the LIFE Act Amendments. The Director will provide the...

  10. New Data on Vaccine Antigen Deficient Bordetella pertussis Isolates

    PubMed Central

    Bouchez, Valérie; Hegerle, Nicolas; Strati, Francesco; Njamkepo, Elisabeth; Guiso, Nicole

    2015-01-01

    Evolution of Bordetella pertussis is driven by natural and vaccine pressures. Isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. Furthermore, during the last epidemics reported in regions using pertussis acellular vaccines, isolates deficient for vaccine antigens, such as pertactin (PRN), were reported to reach high proportions of circulating isolates. More sporadic filamentous hemagglutinin (FHA) or pertussis toxin (PT) deficient isolates were also collected. The whole genome of some recent French isolates, deficient or non-deficient in vaccine antigens, were analyzed. Transcription profiles of the expression of the main virulence factors were also compared. The invasive phenotype in an in vitro human tracheal epithelial (HTE) cell model of infection was evaluated. Our genomic analysis focused on SNPs related to virulence genes known to be more likely to present allelic polymorphism. Transcriptomic data indicated that isolates circulating since the introduction of pertussis vaccines present lower transcription levels of the main virulence genes than the isolates of the pre-vaccine era. Furthermore, isolates not producing FHA present significantly higher expression levels of the entire set of genes tested. Finally, we observed that recent isolates are more invasive in HTE cells when compared to the reference strain, but no multiplication occurs within cells. PMID:26389958

  11. Acute suppurative parotitis in a 33-day-old patient.

    PubMed

    Avcu, Gulhadiye; Belet, Nursen; Karli, Arzu; Sensoy, Gulnar

    2015-06-01

    Acute suppurative parotitis is a rare disease in childhood. Its incidence is higher in premature newborns. Parotid swelling and pus drainage from Stenson's duct is pathognomonic, and Staphylococcus aureus is the causative agent in most cases. Here, a 33-day-old patient with acute suppurative parotitis is presented. PMID:25825340

  12. Glycoprotein A33 deficiency: a new mouse model of impaired intestinal epithelial barrier function and inflammatory disease

    PubMed Central

    Williams, Benjamin B.; Tebbutt, Niall C.; Buchert, Michael; Putoczki, Tracy L.; Doggett, Karen; Bao, Shisan; Johnstone, Cameron N.; Masson, Frederick; Hollande, Frederic; Burgess, Antony W.; Scott, Andrew M.; Ernst, Matthias; Heath, Joan K.

    2015-01-01

    ABSTRACT The cells of the intestinal epithelium provide a selectively permeable barrier between the external environment and internal tissues. The integrity of this barrier is maintained by tight junctions, specialised cell-cell contacts that permit the absorption of water and nutrients while excluding microbes, toxins and dietary antigens. Impairment of intestinal barrier function contributes to multiple gastrointestinal disorders, including food hypersensitivity, inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Glycoprotein A33 (GPA33) is an intestinal epithelium-specific cell surface marker and member of the CTX group of transmembrane proteins. Roles in cell-cell adhesion have been demonstrated for multiple CTX family members, suggesting a similar function for GPA33 within the gastrointestinal tract. To test a potential requirement for GPA33 in intestinal barrier function, we generated Gpa33−/− mice and subjected them to experimental regimens designed to produce food hypersensitivity, colitis and CAC. Gpa33−/− mice exhibited impaired intestinal barrier function. This was shown by elevated steady-state immunosurveillance in the colonic mucosa and leakiness to oral TRITC-labelled dextran after short-term exposure to dextran sodium sulphate (DSS) to injure the intestinal epithelium. Gpa33−/− mice also exhibited rapid onset and reduced resolution of DSS-induced colitis, and a striking increase in the number of colitis-associated tumours produced by treatment with the colon-specific mutagen azoxymethane (AOM) followed by two cycles of DSS. In contrast, Gpa33−/− mice treated with AOM alone showed no increase in sporadic tumour formation, indicating that their increased tumour susceptibility is dependent on inflammatory stimuli. Finally, Gpa33−/− mice displayed hypersensitivity to food allergens, a common co-morbidity in humans with IBD. We propose that Gpa33−/− mice provide a valuable model to study the mechanisms linking intestinal permeability and multiple inflammatory pathologies. Moreover, this model could facilitate preclinical studies aimed at identifying drugs that restore barrier function. PMID:26035389

  13. The Structure of the Poxvirus A33 Protein Reveals a Dimer of Unique C-Type Lectin-Like Domains

    SciTech Connect

    Su, Hua-Poo; Singh, Kavita; Gittis, Apostolos G.; Garboczi, David N.

    2010-11-03

    The current vaccine against smallpox is an infectious form of vaccinia virus that has significant side effects. Alternative vaccine approaches using recombinant viral proteins are being developed. A target of subunit vaccine strategies is the poxvirus protein A33, a conserved protein in the Chordopoxvirinae subfamily of Poxviridae that is expressed on the outer viral envelope. Here we have determined the structure of the A33 ectodomain of vaccinia virus. The structure revealed C-type lectin-like domains (CTLDs) that occur as dimers in A33 crystals with five different crystal lattices. Comparison of the A33 dimer models shows that the A33 monomers have a degree of flexibility in position within the dimer. Structural comparisons show that the A33 monomer is a close match to the Link module class of CTLDs but that the A33 dimer is most similar to the natural killer (NK)-cell receptor class of CTLDs. Structural data on Link modules and NK-cell receptor-ligand complexes suggest a surface of A33 that could interact with viral or host ligands. The dimer interface is well conserved in all known A33 sequences, indicating an important role for the A33 dimer. The structure indicates how previously described A33 mutations disrupt protein folding and locates the positions of N-linked glycosylations and the epitope of a protective antibody.

  14. The MICE luminosity monitor

    NASA Astrophysics Data System (ADS)

    Dobbs, A.; Forrest, D.; Soler, F. J. P.

    2013-02-01

    The MICE experiment will provide the first measurement of ionisation cooling, a technique suitable for reducing the transverse emittance of a tertiary muon beam in a future neutrino factory accelerator facility. MICE is presently in the final stages of commissioning its beam line. The MICE luminosity monitor has proved an invaluable tool throughout this process, providing independent measurements of particle rate from the MICE target, normalisation for beam line detectors and verification of simulation codes.

  15. Morphological study of three Abell's planetary nebulae - A33, A36, and A79

    NASA Astrophysics Data System (ADS)

    Hua, C. T.; Nguyen-Trong, T.

    1983-01-01

    The Abell list discovered in the Palomar Sky Survey includes the three objects A33, A36 and A79, which have been classified as old planetary nebulae. The monochromatic images of these three objects in H-alpha, H-beta, and the forbidden lines N II 6584 A and S II 6717 A, are presented and discussed. The forbidden line N II/H-alpha intensity ratio is found to be useful because of its implications in the evolutionary behavior of planetary nebulae.

  16. Generation of Transgenic Mice

    PubMed Central

    Cho, Andrew; Haruyama, Naoto; Kulkarni, Ashok B.

    2009-01-01

    This unit describes detailed step-by-step protocols, reagents, and equipment required for successful generation of transgenic mice using pronuclear injection. The experimental methods and practical tips given here will help guide beginners in understanding what is required and what to avoid in these standard protocols for efficiently generating transgenic mice. PMID:19283729

  17. A 33-year-old Haitian immigrant with 7 months of abdominal pain and progressive distension

    PubMed Central

    Farhadian, Shelli; Shenoi, Sheela V; Villanueva, Merceditas S

    2015-01-01

    SUMMARY We report a case of a 33-year-old previously healthy Haitian immigrant with a 7-month history of abdominal pain, fever and ascites. He had a history of positive tuberculin skin test but never underwent treatment for latent tuberculosis (TB) infection. Initial examination showed abdominal distension. Abdominal CT scan showed mild ascites, abnormal soft tissue in the greater omentum and small bowel mesentery, retroperitoneal adenopathy, peritoneal thickening and dilated loops of small bowel. Paracentesis and thoracentesis were initially non-diagnostic. HIV testing was negative. The differential diagnosis included lymphoma and TB peritonitis. The omental mass was biopsied under ultrasound guidance, and histopathology revealed non-necrotising granulomas. Sputum cultures and omental biopsy cultures subsequently grew Mycobacterium tuberculosis, and a diagnosis was made of pulmonary TB with TB peritonitis. The patient responded well to the initiation of anti-TB treatment. PMID:25008341

  18. X-linked insertion/deletion polymorphisms: forensic applications of a 33-markers panel.

    PubMed

    Freitas, Natalle S C; Resque, Rafael L; Ribeiro-Rodrigues, Elzemar M; Guerreiro, João F; Santos, Ney P C; Ribeiro-dos-Santos, Andrea; Santos, Sidney

    2010-11-01

    Insertion/deletion (INDEL) polymorphisms are diallelic markers with potential characteristics for use in forensics and biological anthropology, including: the simplicity of laboratory analysis, the possibility of genotyping many markers in a single PCR multiplex reaction, as well as analyzing markers with special inheritance types, such as those linked to the X chromosome (X-INDEL). In this work we developed a laboratory analysis methodology using a 33-INDEL marker panel for the X chromosome in a single PCR multiplex reaction, followed by a capillary electrophoresis run. We employed the panel to genotype a sample of 351 individuals of a mixed population from the Brazilian Amazon. The results demonstrate that the measurement of biostatistical parameters for forensic use in this population is compatible with prior estimates from other populations using current X-STR panels. PMID:20354713

  19. Anterior segment developmental anomalies in a 33-week-old fetus with MIDAS syndrome.

    PubMed

    Herwig, Martina C; Loeffler, Karin U; Gembruch, Ulrich; Kuchelmeister, Klaus; Müller, Annette M

    2014-01-01

    We report anterior segment abnormalities in both eyes of a 33-week-old fetus endorsing the diagnosis of MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome. After abortion, the fetus was examined by a standard pediatric autopsy that included macroscopic and microscopic examination of both eyes. Postmortem findings included craniofacial stigmata (such as hypertelorism, a flat nose and low-set ears) and an agenesis of the corpus callosum. Array comparative genomic hybridization revealed a deletion of the short arm of the X chromosome (region Xp22.2 to p22.32). Ophthalmopathologic examination of the eyes revealed microphthalmia with anterior segment developmental anomalies, in particular sclerocornea and Peters' anomaly, respectively. General pathology findings plus the ocular findings allowed the diagnosis of MIDAS syndrome. A discussion of differential diagnoses is provided. This case report indicates that ophthalmopathologic investigation of fetal eyes can be of great value for the further classification of syndromes. PMID:25291437

  20. Quantitative intratumoural microdistribution and kinetics of 131I-huA33 antibody in patients with colorectal carcinoma

    PubMed Central

    2014-01-01

    Background The ability of recombinant antibodies to adequately penetrate into tumours is a key factor in achieving therapeutic effect; however, the behaviour of antibodies at a cellular level in tumours is poorly understood. The purpose of this study was to investigate those factors that influence the macroscopic and microscopic intratumoural distribution of an IgG1-humanized antibody, huA33, in colorectal tumours. Methods Twelve patients were infused with radiolabelled huA33 at 7 days prior to elective surgery for colorectal carcinoma. Macroscopic huA33 uptake was determined by both gamma well counter and autoradiography measurements of the resected tumour specimens. Microscopic uptake was then quantitated at a cellular level and compared to vascular penetrance. The impact of variation in tumour antigen (GPA33) expression, tumour size, specimen type (primary vs metastatic), presence of macroscopic necrosis, and tumour vasculature on huA33 uptake were examined. Results The I-huA33 uptake in whole tumour sections was (mean ± SD) 5.13 ± 2.71 × 10−3% injected dose per gram (ID/g). GPA33 was expressed in all viable tumour cells, and huA33 uptake was excellent regardless of tumour size and specimen type. In tumours with macroscopically evident central necrosis (n = 5), huA33 uptake in tumour necrotic centres was lower than in viable peripheries (0.606 ± 0.493 vs 2.98 ± 2.17 × 10−3%ID, p = 0.06). However, when corrected for low cell viability in necrotic centres, uptake of huA33 at the cellular level was highly comparable to that in the more viable tumour periphery (7.10 ± 5.10 × 10−9 vs 3.82 ± 3.67 × 10−9%ID/cell, p = 0.4). In the five patients who exhibited macroscopic necrosis in their tumours, huA33 showed excellent tissue penetration, with a maximum penetration distance of 26 μm in peripheral tumour regions and 118 μm in central regions. No correlation was observed between 131I-huA33 uptake in tumour on a cellular basis and tumour vascularity. Conclusions In patients with colorectal carcinoma, monoclonal antibody huA33 effectively targets viable tumour cells in all cellular milieus examined, including effective penetration into necrotic tumour centres, a novel and therapeutically important finding. PMID:24995151

  1. Bochdalek hernia and repetitive pancreatitis in a 33 year old woman

    PubMed Central

    Angel, Medina Andrade Luis; David, Coot Polanco Reyes; Laura, Medina Andrade; Abraham, Medina Andrade; Stephanie, Serrano Collazos; Grecia, Ortiz Ramirez

    2014-01-01

    INTRODUCTION Bochdalek hernia presentation in adulthood is rare. The presentation in newborns is the most common, manifesting with data from respiratory failure secondary to pulmonary hypoplasia, requiring urgent surgical intervention with high morbidity and mortality. PRESENTATION OF CASE We present the case of a 33 year old woman admitted in the emergency room with severe abdominal pain in the left upper quadrant and disnea. After physical examination and laboratory test we diagnose mild acute pancreatitis. The patient haven’t colelitiasis by ulstrasound or any risk factor for pancreatitis. Initially she received medical treatment and was discharged after one week. After four weeks she presented the same symptoms in two different occasions, with severe and mild pancreatitis respectively. A computed tomography report a left posterolateral diafragmatic hernia. In spite of the rare association of pancreatitis and Bochdalek hernia, we realized it as the etiology until the second event and planned his surgery. We made a posterolateral torachotomy and diafragmatic plasty with a politetrafluoroetileno mesh and after a 6 months follow up she has coursed asymptomatic. DISCUSSION The high rate of complications in this type of hernia requires us to perform surgical treatment as the hernia is detected. In this case it is prudent medical treatment prior to surgical correction despite this being the origin of the pancreatitis, because the systemic inflammatory response added by the surgical act could result in a higher rate of complications if not performed at the appropriate time. There is no precise rule to determine the type of approach of choice in this type of hernia which thoracotomy or laparotomy may be used. CONCLUSION Bochdalek hernia is a rare find in adults who require treatment immediately after diagnosis because of the high risk of complications. When presented with data from pancreatitis is recommended to complete the medical treatment of pancreatitis before surgery to obtain the best results, unless it exist another abdominal complication. PMID:25222941

  2. Antinuclear antibodies in mice

    PubMed Central

    Teague, P. O.; Friou, G. J.

    1969-01-01

    Seven-week-old and 16-week-old A/Jax mice were injected with viable spleen cells or homogenates of spleen cells obtained from older syngeneic mice which either had autoimmune anti-deoxyribonucleoprotein (DNP) antibody in their sera or lacked this activity. None of the 7-week-old recipients developed detectable anti-DNP antibody. However, most of the animals in the 16-week-old group developed this autoantibody. The viability of the cells and the presence of or absence of anti-DNP antibody in the donor's sera did not appear to influence the autoimmune response of these recipients. When viable thymus cells which were obtained from young A/Jax mice were transferred to groups of older syngeneic animals that had developed anti-DNP antibody spontaneously, the anti-DNP decreased or disappeared from the sera of most recipients. Untreated controls did not show this variation. When 36-week-old A/Jax mice which lacked anti-DNP antibody were injected with thymus or spleen cells obtained from young donors, none of the recipients or untreated controls developed anti-DNP antibody. After specific immunization with DNP, however, the control animals began to produce autoimmune anti-DNP antibody while the animals treated with thymus or spleen cells remained unresponsive. These observations support the hypothesis that in A/Jax mice: (1) autoimmunity to DNP may result from failure of normal homeostasis mechanisms which allow proliferation of autoimmune cells; (2) the number of cells with autoimmune potential may increase during ageing; (3) the efficiency of the homeostasis system may decrease during ageing as the result of microbial or genetic factors; and (4) cells which participate in homeostasis are found in the thymus and spleen of young mice and may be the thymus dependent lymphocytes. PMID:5307745

  3. The MICE experiment

    NASA Astrophysics Data System (ADS)

    Edgecock, Rob

    2003-08-01

    One of the most important requirements for a neutrino factory and a muon collider is the ability to cool the muons to increase the phase space density. As all existing cooling techniques do not work for muons, a new method has been proposed: ionization cooling. As this is a completely unproven technique, a series of experiments is being built to investigate the cooling process in some detail. MICE is the last and biggest of these and is being designed to show that ionization cooling works and to learn more about the cooling process itself. This paper describes MICE in some detail and outlines its expected performance in measuring cooling.

  4. Colorful Kindergarten Mice

    ERIC Educational Resources Information Center

    Bobick, Bryna; Wheeler, Elizabeth

    2008-01-01

    Developing kindergarten lessons can be very challenging, especially at the beginning of the school year when many students are just learning to cut paper and hold crayons. The author's favorite beginning unit of the year is "mice paintings," a practical introduction to drawing, color theory, and painting. This unit also incorporates children's

  5. Colorful Kindergarten Mice

    ERIC Educational Resources Information Center

    Bobick, Bryna; Wheeler, Elizabeth

    2008-01-01

    Developing kindergarten lessons can be very challenging, especially at the beginning of the school year when many students are just learning to cut paper and hold crayons. The author's favorite beginning unit of the year is "mice paintings," a practical introduction to drawing, color theory, and painting. This unit also incorporates children's…

  6. Mice and Men.

    ERIC Educational Resources Information Center

    Willingham, Shively; Thompson, Charles L.

    Observations and experiments with mice, developed and tested at the Pennsylvania Advancement School with underachieving boys in grades seven and eight, are described in this teachers' guide which includes copies of student worksheets for exercises needing them. In addition to lists of materials and procedural suggestions, ideas for guiding…

  7. Status of MICE

    NASA Astrophysics Data System (ADS)

    Soler, F. J. P.

    2010-03-01

    The Muon Ionization Cooling Experiment (MICE) is an experiment currently under construction at the Rutherford Appleton Laboratory (RAL) in the UK. The aim of the experiment is to demonstrate the concept of ionization cooling for a beam of muons, crucial for the requirements of a Neutrino Factory and a Muon Collider. Muon cooling is achieved by measuring the reduction of the four dimensional transverse emittance for a beam of muons passing through low density absorbers and then accelerating the longitudinal component of the momentum using RF cavities. The absorbers are maintained in a focusing magnetic field to reduce the beta function of the beam and the RF cavities are kept inside coupling coils. The main goal of MICE is to measure a fractional drop in emittance, of order -10% for large emittance beams, with an accuracy of 1% (which imposes a requirement that the absolute emittance be measured with an accuracy of 0.1%). This paper will discuss the status of MICE, including the progress in commissioning the muon beam line at the ISIS accelerator at RAL, the construction of the different detector elements in MICE and the prospects for the future.

  8. Status of MICE

    SciTech Connect

    Soler, F. J. P.

    2010-03-30

    The Muon Ionization Cooling Experiment (MICE) is an experiment currently under construction at the Rutherford Appleton Laboratory (RAL) in the UK. The aim of the experiment is to demonstrate the concept of ionization cooling for a beam of muons, crucial for the requirements of a Neutrino Factory and a Muon Collider. Muon cooling is achieved by measuring the reduction of the four dimensional transverse emittance for a beam of muons passing through low density absorbers and then accelerating the longitudinal component of the momentum using RF cavities. The absorbers are maintained in a focusing magnetic field to reduce the beta function of the beam and the RF cavities are kept inside coupling coils. The main goal of MICE is to measure a fractional drop in emittance, of order -10% for large emittance beams, with an accuracy of 1%(which imposes a requirement that the absolute emittance be measured with an accuracy of 0.1%). This paper will discuss the status of MICE, including the progress in commissioning the muon beam line at the ISIS accelerator at RAL, the construction of the different detector elements in MICE and the prospects for the future.

  9. Mice Drawer System

    NASA Technical Reports Server (NTRS)

    Cancedda, Ranieri

    2008-01-01

    The Mice Drawer System (MDS) is an Italian Space Agency (ASI) facility which is able to support mice onboard the International Space Station during long-duration exploration missions (from 100 to 150-days) by living space, food, water, ventilation and lighting. Mice can be accommodated either individually (maximum 6) or in groups (4 pairs). MDS is integrated in the Space Shuttle middeck during transportation (uploading and downloading) to the ISS and in an EXPRESS Rack in Destiny, the US Laboratory during experiment execution. Osteoporosis is a debilitating disease that afflicts millions of people worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton. This bone loss experienced by astronauts is similar to osteoporosis in the elderly population. MDS will help investigate the effects of unloading on transgenic (foreign gene that has been inserted into its genome to exhibit a particular trait) mice with the Osteoblast Stimulating Factor-1, OSF-1, a growth and differentiation factor, and to study the genetic mechanisms underlying the bone mass pathophysiology. MDS will test the hypothesis that mice with an increased bone density are likely to be more protected from osteoporosis, when the increased bone mass is a direct effect of a gene involved in skeletogenesis (skeleton formation). Osteoporosis is a debilitating disease that afflicts millions worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton, a loss that is similar to osteoporosis in the elderly population on Earth. Osteoblast Stimulating Factor-1 (OSF-1), also known as pleiotrophin (PTN) or Heparin-Binding Growth- Associated Molecule (HB-GAM) belongs to a family of secreted heparin binding proteins..OSF-1 is an extracellular matrix-associated growth and differentiation factor that is normally expressed in cartilage; it can stimulate the proliferation and differentiation of human osteoprogenitor cells (cell that differentiate into an osteoblast) in vitro. The Mice Drawer System will study the effects of microgravity on transgenic mouse bones in order to identify genetic mechanisms playing a role in the reduction of the bone mass observed in humans and animals as a consequence of long-duration (greater than 100 days) microgravity exposure. Onboard the ISS, MDS is relatively self-sufficient; a crewmember will check the health status of the rodents on a daily basis, by assessing them through the viewing window. Water levels will be assessed by the crew daily and refilled as needed. Replacement of the food bars and replacement of the waste filters will be conducted inflight by crewmembers every 20-days.

  10. Partial Return Yoke for MICE

    SciTech Connect

    Witte H.; Plate, S; ,

    2013-05-03

    The international Muon Ionization Cooling Experiment (MICE) is a large scale experiment which is presently assembled at the Rutherford Appleton Laboratory in Didcot, UK. The purpose of MICE is to demonstrate the concept of ionization cooling experimentally. Ionization cooling is an important accelerator concept which will be essential for future HEP experiments such as a potential Muon Collider or a Neutrino Factory. The MICE experiment will house up to 18 superconducting solenoids, all of which produce a substantial amount of magnetic flux. Recently it was realized that this magnetic flux leads to a considerable stray magnetic field in the MICE hall. This is a concern as technical equipment in the MICE hall may may be compromised by this. In July 2012 a concept called partial return yoke was presented to the MICE community, which reduces the stray field in the MICE hall to a safe level. This report summarizes the general concept, engineering considerations and the expected shielding performance.

  11. The concentration of phosphatidylethanolamine in mitochondria can modulate ATP production and glucose metabolism in mice.

    PubMed

    van der Veen, Jelske N; Lingrell, Susanne; da Silva, Robin P; Jacobs, Ren L; Vance, Dennis E

    2014-08-01

    Phosphatidylethanolamine (PE) N-methyltransferase (PEMT) catalyzes the synthesis of phosphatidylcholine (PC) in the liver. Mice lacking PEMT are protected against diet-induced obesity and insulin resistance. We investigated the role of PEMT in hepatic carbohydrate metabolism in chow-fed mice. A pyruvate tolerance test revealed that PEMT deficiency greatly attenuated gluconeogenesis. The reduction in glucose production was specific for pyruvate; glucose production from glycerol was unaffected. Mitochondrial PC levels were lower and PE levels were higher in livers from Pemt(-/-) compared with Pemt(+/+) mice, resulting in a 33% reduction of the PC-to-PE ratio. Mitochondria from Pemt(-/-) mice were also smaller and more elongated. Activities of cytochrome c oxidase and succinate reductase were increased in mitochondria of Pemt(-/-) mice. Accordingly, ATP levels in hepatocytes from Pemt(-/-) mice were double that in Pemt(+/+) hepatocytes. We observed a strong correlation between mitochondrial PC-to-PE ratio and cellular ATP levels in hepatoma cells that expressed various amounts of PEMT. Moreover, mitochondrial respiration was increased in cells lacking PEMT. In the absence of PEMT, changes in mitochondrial phospholipids caused a shift of pyruvate toward decarboxylation and energy production away from the carboxylation pathway that leads to glucose production. PMID:24677714

  12. MICE Staging and Status

    NASA Astrophysics Data System (ADS)

    Hanlet, Pierrick

    2010-03-01

    Ionization cooling will be a key technique for a high-intensity Neutrino Factory or Muon Collider. The Muon Ionization Cooling Experiment (MICE) is a high-precision, staged accelerator experiment being performed at Rutherford Appleton Laboratory in the UK. Its goal is the first demonstration, with 0.1% resolution, of the feasibility of reducing the transverse emittance of a beam of muons by ionization cooling in low-Z absorbers. MICE is being staged in the following steps: I. Creating and characterizing a beam of muons; II. Measuring their emittance; III. Systematic comparison of successive measurements; IV. Inserting absorber; V. Reaccelerating longitudinally; and VI. Complete "10%-cooling" test. Step I is currently in progress with Step II to commence next year; completion of Step VI is anticipated in ˜2012.

  13. Pheromone sensing in mice.

    PubMed

    Rodriguez, I; Boehm, U

    2009-01-01

    Beginning with the neuroepithelium of the vomeronasal organ, the accessory olfactory system in rodents runs parallel to the main olfactory system and is specialized in the detection of pheromones. Only a small number of vomeronasal agonists carrying pheromonal information have been identified this far. These structurally diverse classes of chemicals include peptides secreted by exocrine glands and range from small volatile molecules to proteins and fragments thereof present in urine. Most pheromones activate both vomeronasal and main olfactory sensory neurons, making the identification of functionally relevant populations of sensory neurons difficult. Analyses of gene-targeted mice selectively affecting either vomeronasal or main olfactory signaling have attempted to elucidate the functional contribution of the different chemosensory epithelia to pheromone sensing in mice. These mouse models suggest that both the main and the accessory olfactory systems can converge and synergize to express the complex array of stereotyped behaviors and hormonal changes triggered by pheromones. PMID:19083125

  14. Experimental Paracoccidioidomycosis in Mice

    PubMed Central

    Linares, Leonor I.; Friedman, Lorraine

    1972-01-01

    Virulence and infectivity of nine strains of Paracoccidioides brasiliensis were investigated in groups of mice which were inoculated intranasally or intravenously, and some of each were treated with corticosteroids. Fatal infections were not often seen among untreated mice, but mortality usually occurred when corticosteroids were given, regardless of the route of fungus inoculation. Prior treatment did not uniformly increase the incidence of infection, however; only in the case of intranasally inoculated mice was this effect seen. Most strains appeared to be more virulent when administered intravenously, with the exception of a single strain which, under the influence of corticosteroids, repeatedly displayed greatest virulence when given intranasally. All animals that died early in the course of the disease, irrespective of route of inoculation, always had acute pulmonary lesions and usually no other organ was involved. Animals which died later or were sacrificed always had chronic lung lesions. Whether or not chronically diseased animals had additional organ involvement correlated with how the organisms were administered; intravenously inoculated animals usually had extrapulmonary as well as pulmonary lesions, but lesions of those inoculated intranasally were almost exclusively pulmonary. Corticosteroids did not alter the histologic characteristics of either the acute or the chronic type of lesion, but the lesions of treated animals were usually more extensive. Most of the survivors appeared healthy even when infection was extensive. Images PMID:4637603

  15. Paroxysmal Dyskinesias in Mice

    PubMed Central

    Shirley, Thomas L.; Rao, Lekha M.; Hess, Ellen J.; Jinnah, H. A.

    2009-01-01

    Animal models of human disease are important tools for revealing the underlying mechanisms of pathophysiology and developing therapeutic strategies. Several unique mouse calcium channel mutants have been identified with nonepileptic, episodic dyskinetic movements that are phenotypically similar to human paroxysmal dyskinesias. In this report, video demonstrations of these motor attacks are provided for two previously described mouse mutants, tottering and lethargic, as well as a new one, rocker. Semiquantitative comparisons using two different rating scales reveal differences in attack morphology, severity, and duration among the strains. These mice provide three independent models of paroxysmal dyskinesia and support for prior proposals that channelopathies may underlie the human disorders. PMID:17999434

  16. A hypermorphic epithelial β-catenin mutation facilitates intestinal tumorigenesis in mice in response to compounding WNT-pathway mutations

    PubMed Central

    Buchert, Michael; Rohde, Franziska; Eissmann, Moritz; Tebbutt, Niall; Williams, Ben; Tan, Chin Wee; Owen, Alexander; Hirokawa, Yumiko; Gnann, Alexandra; Orend, Gertraud; Orner, Gayle; Dashwood, Rod H.; Heath, Joan K.; Ernst, Matthias; Janssen, Klaus-Peter

    2015-01-01

    ABSTRACT Activation of the Wnt/β-catenin pathway occurs in the vast majority of colorectal cancers. However, the outcome of the disease varies markedly from individual to individual, even within the same tumor stage. This heterogeneity is governed to a great extent by the genetic make-up of individual tumors and the combination of oncogenic mutations. In order to express throughout the intestinal epithelium a degradation-resistant β-catenin (Ctnnb1), which lacks the first 131 amino acids, we inserted an epitope-tagged ΔN(1-131)-β-catenin-encoding cDNA as a knock-in transgene into the endogenous gpA33 gene locus in mice. The resulting gpA33ΔN-Bcat mice showed an increase in the constitutive Wnt/β-catenin pathway activation that shifts the cell fate towards the Paneth cell lineage in pre-malignant intestinal epithelium. Furthermore, 19% of all heterozygous and 37% of all homozygous gpA33ΔN-Bcat mice spontaneously developed aberrant crypt foci and adenomatous polyps, at frequencies and latencies akin to those observed in sporadic colon cancer in humans. Consistent with this, the Wnt target genes, MMP7  and Tenascin-C, which are most highly expressed in benign human adenomas and early tumor stages, were upregulated in pre-malignant tissue of gpA33ΔN-Bcat mice, but those Wnt target genes associated with excessive proliferation (i.e. Cdnn1, myc) were not. We also detected diminished expression of membrane-associated α-catenin and increased intestinal permeability in gpA33ΔN-Bcat mice in challenge conditions, providing a potential explanation for the observed mild chronic intestinal inflammation and increased susceptibility to azoxymethane and mutant Apc-dependent tumorigenesis. Collectively, our data indicate that epithelial expression of ΔN(1-131)-β-catenin in the intestine creates an inflammatory microenvironment and co-operates with other mutations in the Wnt/β-catenin pathway to facilitate and promote tumorigenesis. PMID:26398937

  17. A hypermorphic epithelial β-catenin mutation facilitates intestinal tumorigenesis in mice in response to compounding WNT-pathway mutations.

    PubMed

    Buchert, Michael; Rohde, Franziska; Eissmann, Moritz; Tebbutt, Niall; Williams, Ben; Tan, Chin Wee; Owen, Alexander; Hirokawa, Yumiko; Gnann, Alexandra; Orend, Gertraud; Orner, Gayle; Dashwood, Rod H; Heath, Joan K; Ernst, Matthias; Janssen, Klaus-Peter

    2015-11-01

    Activation of the Wnt/β-catenin pathway occurs in the vast majority of colorectal cancers. However, the outcome of the disease varies markedly from individual to individual, even within the same tumor stage. This heterogeneity is governed to a great extent by the genetic make-up of individual tumors and the combination of oncogenic mutations. In order to express throughout the intestinal epithelium a degradation-resistant β-catenin (Ctnnb1), which lacks the first 131 amino acids, we inserted an epitope-tagged ΔN(1-131)-β-catenin-encoding cDNA as a knock-in transgene into the endogenous gpA33 gene locus in mice. The resulting gpA33(ΔN-Bcat) mice showed an increase in the constitutive Wnt/β-catenin pathway activation that shifts the cell fate towards the Paneth cell lineage in pre-malignant intestinal epithelium. Furthermore, 19% of all heterozygous and 37% of all homozygous gpA33(ΔN-Bcat) mice spontaneously developed aberrant crypt foci and adenomatous polyps, at frequencies and latencies akin to those observed in sporadic colon cancer in humans. Consistent with this, the Wnt target genes, MMP7 and Tenascin-C, which are most highly expressed in benign human adenomas and early tumor stages, were upregulated in pre-malignant tissue of gpA33(ΔN-Bcat) mice, but those Wnt target genes associated with excessive proliferation (i.e. Cdnn1, myc) were not. We also detected diminished expression of membrane-associated α-catenin and increased intestinal permeability in gpA33(ΔN-Bcat) mice in challenge conditions, providing a potential explanation for the observed mild chronic intestinal inflammation and increased susceptibility to azoxymethane and mutant Apc-dependent tumorigenesis. Collectively, our data indicate that epithelial expression of ΔN(1-131)-β-catenin in the intestine creates an inflammatory microenvironment and co-operates with other mutations in the Wnt/β-catenin pathway to facilitate and promote tumorigenesis. PMID:26398937

  18. Cocaethylene hepatotoxicity in mice.

    PubMed

    Roberts, S M; Roth, L; Harbison, R D; James, R C

    1992-05-01

    Cocaethylene is a novel metabolite of cocaine formed in the presence of ethanol. When administered to ICR male mice in dosages ranging from 10 to 50 mg/kg, i.p., cocaethylene was found to produce dose-dependent hepatic necrosis in the midlobular zone (zone 2). Severity of the lesion was maximal 12-24 hr after administration. A transient but significant decrease in hepatic glutathione content was observed 1 hr after cocaethylene administration. Pretreatment with the cytochrome P450 inhibitors cimetidine (200 mg/kg, i.p., in divided doses) or SKF 525A (50 mg/kg, i.p.) diminished toxicity. Pretreatment of mice with the esterase inhibitor diazinon (10 mg/kg, i.p.) increased cocaethylene hepatotoxicity, as did pretreatment with the cytochrome P450 inducing agents phenobarbital (80 mg/kg/day, i.p., for 3 days) or beta-naphthoflavone (40 mg/kg/day, i.p., for 3 days). Phenobarbital pretreatment also caused a shift in the morphologic site of necrosis from midzonal to peripheral lobular (zone 1) regions. The type of hepatic lesion produced by cocaethylene, its morphologic distribution (including the shift with phenobarbital treatment), the potency of cocaethylene in producing this effect, and the apparent requirement of oxidative metabolism for hepatoxicity were all remarkably similar to observations with its parent compound, cocaine, in this and earlier studies. This suggests that these compounds produce liver toxicity through the same or similar mechanisms. PMID:1596286

  19. Assessing Cognition in Mice.

    PubMed

    Hölter, Sabine M; Garrett, Lillian; Einicke, Jan; Sperling, Bettina; Dirscherl, Petra; Zimprich, Annemarie; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Wurst, Wolfgang

    2015-01-01

    Genetically modified mouse models have proven useful to study learning and memory processes and the neurocircuitry and molecular mechanisms involved, as well as to develop therapies for diseases involving cognitive impairment. A variety of tests have been developed to measure cognition in mice, and here we present those established and regularly used in the German Mouse Clinic. The test paradigms have been carefully chosen according to reliability of results and disease relevance of the cognitive functions assessed. Further criteria were time efficiency and ease of application. All tests assess slightly different but also overlapping or interacting aspects of learning and memory so that they can be used to complement each other in a comprehensive assessment of cognitive function. The five protocols described are for spontaneous alternation in the Y-maze, social discrimination, object recognition, automated assessment of learning and memory using the IntelliCage, and olfactory discrimination learning. PMID:26629775

  20. Transgenic mice: beyond the knockout

    PubMed Central

    2011-01-01

    Transgenic mice have had a tremendous impact on biomedical research. Most researchers are familiar with transgenic mice that carry Cre recombinase (Cre) and how they are used to create conditional knockouts. However, some researchers are less familiar with many of the other types of transgenic mice and their applications. For example, transgenic mice can be used to study biochemical and molecular pathways in primary cultures and cell suspensions derived from transgenic mice, cell-cell interactions using multiple fluorescent proteins in the same mouse, and the cell cycle in real time and in the whole animal, and they can be used to perform deep tissue imaging in the whole animal, follow cell lineage during development and disease, and isolate large quantities of a pure cell type directly from organs. These novel transgenic mice and their applications provide the means for studying of molecular and biochemical events in the whole animal that was previously limited to cell cultures. In conclusion, transgenic mice are not just for generating knockouts. PMID:21068085

  1. The MICE Muon Beam Line

    SciTech Connect

    Apollonio, Marco

    2011-10-06

    In the Muon Ionization Cooling Experiment (MICE) at RAL, muons are produced and transported in a dedicated beam line connecting the production point (target) to the cooling channel. We discuss the main features of the beamline, meant to provide muons with momenta between 140 MeV/c and 240 MeV/c and emittances up to 10 mm rad, which is accomplished by means of a diffuser. Matching procedures to the MICE cooling channel are also described. In summer 2010 we performed an intense data taking campaign to finalize the calibration of the MICE Particle Identification (PID) detectors and the understanding of the beam line, which completes the STEPI phase of MICE. We highlight the main results from these data.

  2. The MICE Muon Beam Line

    NASA Astrophysics Data System (ADS)

    Apollonio, Marco

    2011-10-01

    In the Muon Ionization Cooling Experiment (MICE) at RAL, muons are produced and transported in a dedicated beam line connecting the production point (target) to the cooling channel. We discuss the main features of the beamline, meant to provide muons with momenta between 140 MeV/c and 240 MeV/c and emittances up to 10 mm rad, which is accomplished by means of a diffuser. Matching procedures to the MICE cooling channel are also described. In summer 2010 we performed an intense data taking campaign to finalize the calibration of the MICE Particle Identification (PID) detectors and the understanding of the beam line, which completes the STEPI phase of MICE. We highlight the main results from these data.

  3. Transgenic mice in developmental toxicology

    SciTech Connect

    Woychik, R.P.

    1992-12-31

    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  4. Transgenic mice in developmental toxicology

    SciTech Connect

    Woychik, R.P.

    1992-01-01

    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  5. Mice develop normally without tenascin.

    PubMed

    Saga, Y; Yagi, T; Ikawa, Y; Sakakura, T; Aizawa, S

    1992-10-01

    Tenascin, an extracellular matrix protein, is expressed in an unusually restricted pattern during embryogenesis and has been implicated in a variety of morphogenetic phenomena. To directly assess the function of tenascin in vivo, we generated mutant mice in which the tenascin gene was nully disrupted by replacing it with the lacZ gene. In mutant mice, lacZ was expressed in place of tenascin, and no tenascin product was detected. Homozygous mutant mice were, however, obtained in accordance with Mendelian laws, and both females and males produced offspring normally. No anatomical or histological abnormalities were detected in any tissues, and no major changes were observed in distribution of fibronectin, laminin, collagen, and proteoglycan. The existence of these mutant mice, lacking tenascin yet phenotypically normal, casts doubt on the theory that tenascin plays and essential role in normal development. PMID:1383086

  6. Influence of size, surface, cell line, and kinetic properties on the specific binding of A33 antigen-targeted multilayered particles and capsules to colorectal cancer cells.

    PubMed

    Cortez, Christina; Tomaskovic-Crook, Eva; Johnston, Angus P R; Scott, Andrew M; Nice, Edouard C; Heath, Joan K; Caruso, Frank

    2007-09-01

    There has been increased interest in the use of polymer capsules formed by the layer-by-layer (LbL) technique as therapeutic carriers to cancer cells due to their versatility and ease of surface modification. We have investigated the influence of size, surface properties, cell line, and kinetic parameters such as dosage (particle concentration) and incubation time on the specific binding of humanized A33 monoclonal antibody (huA33 mAb)-coated LbL particles and capsules to colorectal cancer cells. HuA33 mAb binds to the A33 antigen present on almost all colorectal cancer cells and has demonstrated great promise in clinical trials as an immunotherapeutic agent for cancer therapy. Flow cytometry experiments showed the cell binding specificity of huA33 mAb-coated particles to be size-dependent, with the optimal size for enhanced selectivity at approximately 500 nm. The specific binding was improved by increasing the dosage of particles incubated with the cells. The level of specific versus nonspecific binding was compared for particles terminated with various polyelectrolytes to examine the surface dependency of antibody attachment and subsequent cell binding ability. The specific binding of huA33 mAb-coated particles is also reported for two colorectal cancer cell lines, with an enhanced binding ratio between 4 and 10 obtained for the huA33 mAb-functionalized particles. This investigation aims to improve the level of specific targeting of LbL particles, which is important in targeted drug and gene delivery applications. PMID:19206525

  7. Tamoxifen administration to mice.

    PubMed

    Whitfield, Jonathan; Littlewood, Trevor; Soucek, Laura

    2015-03-01

    The strategy of fusing a protein of interest to a hormone-binding domain (HBD) of a steroid hormone receptor allows fine control of the activity of the fused protein. Such fusion proteins are inactive in the absence of ligand, because they are complexed with a variety of intracellular polypeptides. Upon ligand binding, the receptor is released from its inhibitory complex and the fusion protein becomes functional. In the murine estrogen receptor (ER) fusion system, proteins are fused to the HBD of the ER. The system relies on the use of a mutant ER known as ER(TAM). Compared to the wild-type HBD, ER(TAM) has 1000-fold lower affinity for estrogen, yet remains responsive to activation by the synthetic steroid 4-hydroxytamoxifen (4-OHT). Because 4-OHT is expensive, animals can be treated with the cheaper precursor tamoxifen, which is converted into 4-OHT by a liver enzyme. Here we present an overview of the methods used to deliver tamoxifen to mice. The most used method is intraperitoneal injection, because the amount of administered compound can be better controlled, but delivery by oral gavage is also possible. For short-term and immediate-effect studies or when conversion of tamoxifen by the liver is to be avoided, 4-OHT can be used directly. PMID:25734062

  8. Partial hepatectomy in mice.

    PubMed

    Nevzorova, Y A; Tolba, R; Trautwein, C; Liedtke, C

    2015-04-01

    The surgical procedure of two-thirds partial hepatectomy (PH) in rodents was first described more than 80 years ago by Higgins and Anderson. Nevertheless, this technique is still a state-of-the-art method for the community of liver researchers as it allows the in-depth analysis of signalling pathways involved in liver regeneration and hepatocarcinogenesis. The importance of PH as a key method in experimental hepatology has even increased in the last decade due to the increasing availability of genetically-modified mouse strains. Here, we propose a standard operating procedure (SOP) for the implementation of PH in mice, which is based on our experience of more than 10 years. In particular, the SOP offers all relevant background information on the PH model and provides comprehensive guidelines for planning and performing PH experiments. We provide established recommendations regarding optimal age and gender of animals, use of appropriate anaesthesia and biometric calculation of the experiments. We finally present an easy-to-follow step-by-step description of the complete surgical procedure including required materials, critical steps and postoperative management. This SOP especially takes into account the latest changes in animal welfare rules in the European Union but is still in agreement with current international regulations. In summary, this article provides comprehensive information for the legal application, design and implementation of PH experiments. PMID:25835741

  9. Inborn anemias in mice

    SciTech Connect

    Bernstein, S.E.; Barker, J.E.; Russell, E.S.

    1981-06-01

    hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, five hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an ..cap alpha..-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values, (b) determinations of radiosensitivity under a variety of conditions, (c) measurements of iron metabolism and heme synthesis, (d) histological and biochemical study of blood-forming tissue, (e) functional tests of the stem cell component, (f) examination of responses to erythroid stimuli, and (g) transplantation of tissue between individuals of differently affected genotypes.

  10. The MICE Run Control System

    NASA Astrophysics Data System (ADS)

    Hanlet, Pierrick; Mice Collaboration

    2014-06-01

    The Muon Ionization Cooling Experiment (MICE) is a demonstration experiment to prove the feasibility of cooling a beam of muons for use in a Neutrino Factory and/or Muon Collider. The MICE cooling channel is a section of a modified Study II cooling channel which will provide a 10% reduction in beam emittance. In order to ensure a reliable measurement, MICE will measure the beam emittance before and after the cooling channel at the level of 1%, or a relative measurement of 0.001. This renders MICE a precision experiment which requires strict controls and monitoring of all experimental parameters in order to control systematic errors. The MICE Controls and Monitoring system is based on EPICS and integrates with the DAQ, Data monitoring systems, and a configuration database. The new MICE Run Control has been developed to ensure proper sequencing of equipment and use of system resources to protect data quality. A description of this system, its implementation, and performance during recent muon beam data collection will be discussed.

  11. Linkage Disequilibrium in Wild Mice

    PubMed Central

    Laurie, Cathy C; Nickerson, Deborah A; Anderson, Amy D; Weir, Bruce S; Livingston, Robert J; Dean, Matthew D; Smith, Kimberly L; Schadt, Eric E; Nachman, Michael W

    2007-01-01

    Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD) in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1) Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2) they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3) LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits. PMID:17722986

  12. Disparity between levels of in vitro neutralization of vaccinia virus by antibody to the A27 protein and protection of mice against intranasal challenge.

    PubMed

    Fogg, Christiana N; Americo, Jeffrey L; Earl, Patricia L; Resch, Wolfgang; Aldaz-Carroll, Lydia; Eisenberg, Roselyn J; Cohen, Gary H; Moss, Bernard

    2008-08-01

    Immunization with recombinant proteins may provide a safer alternative to live vaccinia virus for prophylaxis of poxvirus infections. Although antibody protects against vaccinia virus infection, the mechanism is not understood and the selection of immunogens is daunting as there are dozens of surface proteins and two infectious forms known as the mature virion (MV) and the enveloped virion (EV). Our previous studies showed that mice immunized with soluble forms of EV membrane proteins A33 and B5 and MV membrane protein L1 or passively immunized with antibodies to these proteins survived an intranasal challenge with vaccinia virus. The present study compared MV protein A27, which has a role in virus attachment to glycosaminoglycans on the cell surface, to L1 with respect to immunogenicity and protection. Although mice developed similar levels of neutralizing antibody after immunizations with A27 or L1, A27-immunized mice exhibited more severe disease upon an intranasal challenge with vaccinia virus. In addition, mice immunized with A27 and A33 were not as well protected as mice receiving L1 and A33. Polyclonal rabbit anti-A27 and anti-L1 IgG had equivalent MV-neutralizing activities when measured by the prevention of infection of human or mouse cells or cells deficient in glycosaminoglycans or by adding antibody prior to or after virus adsorption. Nevertheless, the passive administration of antibody to A27 was poorly protective compared to the antibody to L1. These studies raise questions regarding the basis for antibody protection against poxvirus disease and highlight the importance of animal models for the early evaluation of vaccine candidates. PMID:18524827

  13. Encephalitozoonosis in pharmacologically immunosuppressed mice.

    PubMed

    Anete Lallo, Maria; Porta Miche Hirschfeld, Marisa

    2012-07-01

    Encephalitozoon cuniculi is a parasite that has been identified as a cause of opportunistic infections in immunocompromised individuals. This study was performed to evaluate E. cuniculi infection in pharmacologically immunosuppressed mice. Mice were immunosuppressed with cyclophosphamide (100mg/kg twice a week, IP) or cyclosporin (10mg/kg daily, IP) and inoculated with 10(7)E. cuniculi spores IP. The E. cuniculi spores were cultivated in MDCK cells. E. cuniculi identification was performed by light microscopy studies using Gram-Chromotrope, Hematoxylin-Eosin and Toluidine blue-fuchsin staining techniques, as well as by PCR at 15, 30 and 45 days post-inoculation (DPI). Cyclophosphamide-immunosuppressed mice have greatly reduced amounts of CD8(+), CD4(+) and CD3(+) T cells and CD19(+) B cells. The cells from these mice were analyzed by FACS and showed acute disseminated and fatal encephalitozoonosis. Mice treated with ciclosporin, which is both antiparasitic and immunosuppressive, have a milder, chronic, non-lethal infection and showed a significant reduction only in CD3(+) and CD4(+) T cell numbers. Our results support the role of CD8(+) T cells in controlling infection by E. cuniculi and show that preventive measures are essential for preventing this zoonosis in individuals undergoing chemotherapy for cancer or other immunosuppressive therapies. PMID:22626517

  14. Practical pathology of aging mice.

    PubMed

    Pettan-Brewer, Christina; Treuting, Piper M

    2011-01-01

    Old mice will have a subset of lesions as part of the progressive decline in organ function that defines aging. External and palpable lesions will be noted by the research, husbandry, or veterinary staff during testing, cage changing, or physical exams. While these readily observable lesions may cause alarm, not all cause undue distress or are life-threatening. In aging research, mice are maintained until near end of life that, depending on strain and genetic manipulation, can be upwards of 33 months. Aging research has unique welfare issues related to age-related decline, debilitation, fragility, and associated pain of chronic diseases. An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions. The goal of this paper is to introduce investigators to age-associated diseases and lesion patterns in mice from clinical presentation to pathologic assessment. To do so, we present and illustrate the common clinical appearances, necropsy and histopathological lesions seen in subsets of the aging colonies maintained at the University of Washington. PMID:22953032

  15. HLA-A*33:01 as protective allele for severe dengue in a population of Filipino children.

    PubMed

    Mercado, Edelwisa Segubre; Espino, Fe Esperanza; Perez, Ma Lucila M; Bilar, Josie M; Bajaro, Jemimah Dawn P; Huy, Nguyen Tien; Baello, Benilda Q; Kikuchi, Mihoko; Hirayama, Kenji

    2015-01-01

    Dengue virus infection is a leading cause of morbidity among children in the Philippines in recent years. In order to investigate the association of HLA Class I and II alleles and dengue disease severity in a cohort of Filipino children, we performed a case control study in 2 hospitals in Metro Manila from June 2008 to December 2009. A total of 250 laboratory confirmed dengue patients and 300 healthy individuals aged 5 to 15 years old were typed for HLA-A, B and DRB1 alleles. The frequency of HLA-A*33:01 was significantly decreased in severe dengue (DHF/ DSS; Pc = 0.0016)) and DSS (Pc = 0.0032) compared to the background population. These findings support a previous study that this allele may confer protection against the severe form of dengue and provide the first evidence of HLA association with dengue in the Philippines. Future studies should be directed in investigating the possible mechanisms of protection. PMID:25659158

  16. HLA-A*33:01 as Protective Allele for Severe Dengue in a Population of Filipino Children

    PubMed Central

    Mercado, Edelwisa Segubre; Espino, Fe Esperanza; Perez, Ma. Lucila M.; Bilar, Josie M.; Bajaro, Jemimah Dawn P.; Huy, Nguyen Tien; Baello, Benilda Q; Kikuchi, Mihoko; Hirayama, Kenji

    2015-01-01

    Dengue virus infection is a leading cause of morbidity among children in the Philippines in recent years. In order to investigate the association of HLA Class I and II alleles and dengue disease severity in a cohort of Filipino children, we performed a case control study in 2 hospitals in Metro Manila from June 2008 to December 2009. A total of 250 laboratory confirmed dengue patients and 300 healthy individuals aged 5 to 15 years old were typed for HLA-A, B and DRB1 alleles. The frequency of HLA-A*33:01 was significantly decreased in severe dengue (DHF/ DSS; Pc = 0.0016)) and DSS (Pc = 0.0032) compared to the background population. These findings support a previous study that this allele may confer protection against the severe form of dengue and provide the first evidence of HLA association with dengue in the Philippines. Future studies should be directed in investigating the possible mechanisms of protection. PMID:25659158

  17. Association of a 33-kilodalton cysteine proteinase found in corn callus with the inhibition of fall armyworm larval growth.

    PubMed Central

    Jiang, B; Siregar, U; Willeford, K O; Luthe, D S; Williams, W P

    1995-01-01

    Protein patterns of callus from corn (Zea mays L.) inbreds that are either resistant or susceptible to fall armyworm (Spodoptera frugiperda [J.E. Smith]) were analyzed by two-dimensional electrophoresis. Fall armyworm larvae reared on callus initiated from resistant inbreds were significantly smaller than those reared on callus of susceptible inbreds. A 33-kD protein found in callus from the resistant inbreds Mp704 and Mp708 was absent in callus from the susceptible inbreds Tx601 and Ab24E. However, a 36-kD protein found in Ab24E callus immunoreacted with polyclonal antibody raised against the 33-kD protein. When Mp704 nonfriable callus changed to friable, larval growth was not inhibited and the 33-kD protein was absent. There was a significant negative correlation between the concentration of the 33-kD protein in the callus and the weight of the larvae feeding on the callus in the F2 progeny of Mp704 x Tx601. The N-terminal amino acid sequence of the 33-kD protein suggested that it was cysteine proteinase. Purification of the 33- (Mp708) and 36-kD (Ab24E) proteins indicated that they were both cysteine proteinases. The 33-kD cysteine proteinase had 7-fold higher specific activity than the 36-kD enzyme. PMID:7659755

  18. Liquid Hydrogen Absorber for MICE

    SciTech Connect

    Ishimoto, S.; Suzuki, S.; Yoshida, M.; Green, Michael A.; Kuno, Y.; Lau, Wing

    2010-05-30

    Liquid hydrogen absorbers for the Muon Ionization Cooling Experiment (MICE) have been developed, and the first absorber has been tested at KEK. In the preliminary test at KEK we have successfully filled the absorber with {approx}2 liters of liquid hydrogen. The measured hydrogen condensation speed was 2.5 liters/day at 1.0 bar. No hydrogen leakage to vacuum was found between 300 K and 20 K. The MICE experiment includes three AFC (absorber focusing coil) modules, each containing a 21 liter liquid hydrogen absorber made of aluminum. The AFC module has safety windows to separate its vacuum from that of neighboring modules. Liquid hydrogen is supplied from a cryocooler with cooling power 1.5 W at 4.2 K. The first absorber will be assembled in the AFC module and installed in MICE at RAL.

  19. Voluntary Wheel Running in Mice.

    PubMed

    Goh, Jorming; Ladiges, Warren

    2015-01-01

    Voluntary wheel running in the mouse is used to assess physical performance and endurance and to model exercise training as a way to enhance health. Wheel running is a voluntary activity in contrast to other experimental exercise models in mice, which rely on aversive stimuli to force active movement. This protocol consists of allowing mice to run freely on the open surface of a slanted, plastic saucer-shaped wheel placed inside a standard mouse cage. Rotations are electronically transmitted to a USB hub so that frequency and rate of running can be captured via a software program for data storage and analysis for variable time periods. Mice are individually housed so that accurate recordings can be made for each animal. Factors such as mouse strain, gender, age, and individual motivation, which affect running activity, must be considered in the design of experiments using voluntary wheel running. PMID:26629772

  20. The MICE Particle Identification System

    NASA Astrophysics Data System (ADS)

    Bogomilov, M.; MICE Collaboration

    2011-06-01

    The Muon Ionization Cooling Experiment (MICE) at the ISIS accelerator located at the Rutherford Appleton Laboratory, UK, will be the first experiment to study muon cooling at high precision. Demonstration of muon ionization cooling is a major technological step towards the construction of a neutrino factory or a muon collider. A muon beam is produced via pion decay in the MICE beam line within a range of emittances and momenta. Muon purity is assured by a system of detectors for particle identification (PID). We describe briefly the PID system here.

  1. CYP86A33-Targeted Gene Silencing in Potato Tuber Alters Suberin Composition, Distorts Suberin Lamellae, and Impairs the Periderm's Water Barrier Function1[C][W][OA

    PubMed Central

    Serra, Olga; Soler, Marçal; Hohn, Carolin; Sauveplane, Vincent; Pinot, Franck; Franke, Rochus; Schreiber, Lukas; Prat, Salomé; Molinas, Marisa; Figueras, Mercè

    2009-01-01

    Suberin is a cell wall lipid polyester found in the cork cells of the periderm offering protection against dehydration and pathogens. Its biosynthesis and assembly, as well as its contribution to the sealing properties of the periderm, are still poorly understood. Here, we report on the isolation of the coding sequence CYP86A33 and the molecular and physiological function of this gene in potato (Solanum tuberosum) tuber periderm. CYP86A33 was down-regulated in potato plants by RNA interference-mediated silencing. Periderm from CYP86A33-silenced plants revealed a 60% decrease in its aliphatic suberin load and greatly reduced levels of C18:1 ω-hydroxyacid (approximately 70%) and α,ω-diacid (approximately 90%) monomers in comparison with wild type. Moreover, the glycerol esterified to suberin was reduced by 60% in the silenced plants. The typical regular ultrastructure of suberin, consisting of dark and light lamellae, disappeared and the thickness of the suberin layer was clearly reduced. In addition, the water permeability of the periderm isolated from CYP86A33-silenced lines was 3.5 times higher than that of the wild type. Thus, our data provide convincing evidence for the involvement of ω-functional fatty acids in establishing suberin structure and function. PMID:19109416

  2. CYP86A33-targeted gene silencing in potato tuber alters suberin composition, distorts suberin lamellae, and impairs the periderm's water barrier function.

    PubMed

    Serra, Olga; Soler, Marçal; Hohn, Carolin; Sauveplane, Vincent; Pinot, Franck; Franke, Rochus; Schreiber, Lukas; Prat, Salomé; Molinas, Marisa; Figueras, Mercè

    2009-02-01

    Suberin is a cell wall lipid polyester found in the cork cells of the periderm offering protection against dehydration and pathogens. Its biosynthesis and assembly, as well as its contribution to the sealing properties of the periderm, are still poorly understood. Here, we report on the isolation of the coding sequence CYP86A33 and the molecular and physiological function of this gene in potato (Solanum tuberosum) tuber periderm. CYP86A33 was down-regulated in potato plants by RNA interference-mediated silencing. Periderm from CYP86A33-silenced plants revealed a 60% decrease in its aliphatic suberin load and greatly reduced levels of C18:1 omega-hydroxyacid (approximately 70%) and alpha,omega-diacid (approximately 90%) monomers in comparison with wild type. Moreover, the glycerol esterified to suberin was reduced by 60% in the silenced plants. The typical regular ultrastructure of suberin, consisting of dark and light lamellae, disappeared and the thickness of the suberin layer was clearly reduced. In addition, the water permeability of the periderm isolated from CYP86A33-silenced lines was 3.5 times higher than that of the wild type. Thus, our data provide convincing evidence for the involvement of omega-functional fatty acids in establishing suberin structure and function. PMID:19109416

  3. Emergence of a Virulent Clade of Vibrio vulnificus and Correlation with the Presence of a 33-Kilobase Genomic Island▿

    PubMed Central

    Cohen, Ana Luisa V.; Oliver, James D.; DePaola, Angelo; Feil, Edward J.; Fidelma Boyd, E.

    2007-01-01

    Vibrio vulnificus is a ubiquitous inhabitant of the marine coastal environment, and an important pathogen of humans. We characterized a globally distributed sample of environmental isolates from a range of habitats and hosts and compared these with isolates recovered from cases of human infection. Multilocus sequence typing data using six housekeeping genes divided 63 of the 67 isolates into the two main lineages previously noted for this species, and this division was also confirmed using the 16S rRNA and open reading frame VV0401 markers. Lineage I was comprised exclusively of biotype 1 isolates, whereas lineage II contained biotype 1 and all biotype 2 isolates. Four isolates did not cluster within either lineage: two biotype 3 and two biotype 1 isolates. The proportion of isolates recovered from a clinical setting was noted to be higher in lineage I than in lineage II. Lineage I isolates were also associated with a 33-kb genomic island (region XII), one of three regions identified by genome comparisons as unique to the species. Region XII contained an arylsulfatase gene cluster, a sulfate reduction system, two chondroitinase genes, and an oligopeptide ABC transport system, all of which are absent from the majority of lineage II isolates. Arylsulfatases and the sulfate reduction system, along with performing a scavenging role, have been hypothesized to play a role in pathogenic processes in other bacteria. Our data suggest that lineage I may have a higher pathogenic potential and that region XII, along with other regions, may give isolates a selective advantage either in the human host or in the aquatic environment or both. PMID:17616611

  4. Modified Protein Improves Vitiligo Symptoms in Mice

    MedlinePlus

    ... 2013 (historical) Modified Protein Improves Vitiligo Symptoms in Mice Altering a key protein involved in the development ... pigmentation loss associated with the skin disorder in mice, according to recent research funded by the NIH’s ...

  5. HZE Radiation Leukemogenesis in Mice

    NASA Astrophysics Data System (ADS)

    Peng, Yuanlin

    Radiation exposure is a risk factor for acute myeloid leukemia (AML). The Leukemogenesis NSCOR was developed to compare this risk for low LET vs HZE radiations as a means to better assess the leukemia risk to astronauts posed by space radiation. Individual projects within the NSCOR explore HZE radiation leukemogenesis in murine model systems and extend the findings to AML in humans. AML sensitive CBA/CaJ mice have been irradiated with 1 GeV 56 Fe particles at NSRL and with 137 Cs gamma-rays at Colorado State University and followed to 800 days of age for the development of AML. Molecular and cytogenetic analyses of HZE- and gamma-induced AML, including assays for chromosomal aberrations, PU.1 deletion, gene expression, array CGH and microsatellite instability are ongoing. Preliminary data indicate that 56 Fe particles are no more effective in inducing AML or shortening lifespan than gamma-rays. Studies designed to address the individual molecular steps in leukemogenesis and determine the effects of radiation and genetic background on each step have been initiated using knockout mice. Deletion of the PU.1 gene on mouse chromosome 2 is a critical step in this murine model of radiation leukemogenesis. Two of the three HZE-induced AMLs that could be assayed and thirteen of fourteen γ-induced AMLs had PU.1 loss as determined by Fluorescence in Situ Hybridization (FISH). We have found that AML sensitive CBA/CaJ mice have a higher incidence of Chr. 2 deletion in bone marrow cells following 56 Fe irradiation than AML resistant C57BL/6 mice. This study is being extended to proton irradiated mice. Our preliminary results indicate that microsatellite instability may be common in HZE irradiated progenitor cells. To determine if these cytogenetic changes can be induced in human myeloid progenitor cells by gamma, proton or HZE irradiation we are generating NOD/SCID mice that have been "humanized" by being transplanted with human hematopoietic stem cells. We are currently irradiating the humanized NOD/SCID mice with gamma-rays and then harvesting human cells from their bone marrow. These cells will be assayed for specific cytogenetic and molecular changes consistent with AML. In addition to screening the cells for chromosomal aberrations and specific deletions and translocations, we will also screen them for microsatellite instability by small pool PCR.(Funded by NASA Grant NAG9 1569)

  6. Transplacental arsenic carcinogenesis in mice

    SciTech Connect

    Waalkes, Michael P. Liu, Jie; Diwan, Bhalchandra A.

    2007-08-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from days 8 to 18 of gestation, and the offspring were observed for up to 2 years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans and investigating a potential transplacental component of the human carcinogenic response to arsenic should be a research priority.

  7. Measuring Motor Coordination in Mice

    PubMed Central

    Deacon, Robert M.J.

    2013-01-01

    Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such as emotionality or cognition can be assessed, however, it is vital to determine whether the motor capabilities of e.g. a mutant or lesioned mouse allow such an assessment. Performance on a maze task requiring strength and coordination, such as the Morris water maze, might well be impaired in a mouse by motor, rather than cognitive, impairments, so it is essential to selectively dissect the latter from the former. For example, sensorimotor impairments caused by NMDA antagonists have been shown to impair water maze performance2. Motor coordination has traditionally been assessed in mice and rats by the rotarod test, in which the animal is placed on a horizontal rod that rotates about its long axis; the animal must walk forwards to remain upright and not fall off. Both set speed and accelerating versions of the rotarod are available. The other three tests described in this article (horizontal bar, static rods and parallel bars) all measure coordination on static apparatus. The horizontal bar also requires strength for adequate performance, particularly of the forelimbs as the mouse initially grips the bar just with the front paws. Adult rats do not perform well on tests such as the static rods and parallel bars (personal observations); they appear less well coordinated than mice. I have only tested male rats, however, and male mice seem generally less well coordinated than females. Mice appear to have a higher strength:weight ratio than rats; the Latin name, Mus musculus, seems entirely appropriate. The rotarod, the variations of the foot fault test12 or the Catwalk (Noldus)15 apparatus are generally used to assess motor coordination in rats. PMID:23748408

  8. Measuring motor coordination in mice.

    PubMed

    Deacon, Robert M J

    2013-01-01

    Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such as emotionality or cognition can be assessed, however, it is vital to determine whether the motor capabilities of e.g. a mutant or lesioned mouse allow such an assessment. Performance on a maze task requiring strength and coordination, such as the Morris water maze, might well be impaired in a mouse by motor, rather than cognitive, impairments, so it is essential to selectively dissect the latter from the former. For example, sensorimotor impairments caused by NMDA antagonists have been shown to impair water maze performance(2). Motor coordination has traditionally been assessed in mice and rats by the rotarod test, in which the animal is placed on a horizontal rod that rotates about its long axis; the animal must walk forwards to remain upright and not fall off. Both set speed and accelerating versions of the rotarod are available. The other three tests described in this article (horizontal bar, static rods and parallel bars) all measure coordination on static apparatus. The horizontal bar also requires strength for adequate performance, particularly of the forelimbs as the mouse initially grips the bar just with the front paws. Adult rats do not perform well on tests such as the static rods and parallel bars (personal observations); they appear less well coordinated than mice. I have only tested male rats, however, and male mice seem generally less well coordinated than females. Mice appear to have a higher strength:weight ratio than rats; the Latin name, Mus musculus, seems entirely appropriate. The rotarod, the variations of the foot fault test(12) or the Catwalk (Noldus)(15) apparatus are generally used to assess motor coordination in rats. PMID:23748408

  9. Progress of MICE RFCC Module

    SciTech Connect

    Li, D.; Bowring, D.; DeMello, A.; Gourlay, S.; Green, M.; Li, N.; Niinikoski, T.; Pan, H.; Prestemon, S.; Virostek, S.; Zisman, M.; Bross, A.; Carcagno, R.; Kashikhin, V.; Sylvester, C.; Chen, A.B.; Guo, Bin; Li, Liyi; Xu, Fengyu; Cao, Y.; Sun, S.; Wang, Li; Yin, Lixin; Luo, Tianhuan; Summers, Don; Smith, B.; Radovinsky, A.; Zhukovsky, A.; Kaplan, D.

    2012-05-20

    Recent progress on the design and fabrication of the RFCC (RF and superconducting Coupling Coil) module for the international MICE (Muon Ionization Cooling Experiment) are reported. The MICE ionization cooling channel has two RFCC modules, each having four 201- MHz normal conducting RF cavities surrounded by one superconducting coupling coil (solenoid) magnet. The magnet is designed to be cooled by three cryocoolers. Fabrication of the RF cavities is complete; preparation for the cavity electro-polishing, low power RF measurements, and tuning are in progress at Lawrence Berkeley National Laboratory (LBNL). Fabrication of the cold mass of the first coupling coil magnet has been completed in China and the cold mass arrived at LBNL in late 2011. Preparations for testing the cold mass are currently under way at Fermilab. Plans for the RFCC module assembly and integration are being developed and are described.

  10. Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice.

    PubMed

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss; Wiese, Maria; Lundsager, Mia; Nielsen, Dennis Sandris; Buschard, Karsten Stig; Hansen, Axel Kornerup; Frkir, Hanne

    2016-01-01

    Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND) 1-4 in NOD mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 mice. PMID:26783537

  11. Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice

    PubMed Central

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss; Wiese, Maria; Lundsager, Mia; Buschard, Karsten Stig; Hansen, Axel Kornerup; Frøkiær, Hanne

    2016-01-01

    Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND) 1–4 in NOD mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 mice. PMID:26783537

  12. Trace fear conditioning in mice.

    PubMed

    Lugo, Joaquin N; Smith, Gregory D; Holley, Andrew J

    2014-01-01

    In this experiment we present a technique to measure learning and memory. In the trace fear conditioning protocol presented here there are five pairings between a neutral stimulus and an unconditioned stimulus. There is a 20 sec trace period that separates each conditioning trial. On the following day freezing is measured during presentation of the conditioned stimulus (CS) and trace period. On the third day there is an 8 min test to measure contextual memory. The representative results are from mice that were presented with the aversive unconditioned stimulus (shock) compared to mice that received the tone presentations without the unconditioned stimulus. Trace fear conditioning has been successfully used to detect subtle learning and memory deficits and enhancements in mice that are not found with other fear conditioning methods. This type of fear conditioning is believed to be dependent upon connections between the medial prefrontal cortex and the hippocampus. One current controversy is whether this method is believed to be amygdala-independent. Therefore, other fear conditioning testing is needed to examine amygdala-dependent learning and memory effects, such as through the delay fear conditioning. PMID:24686718

  13. Trace Fear Conditioning in Mice

    PubMed Central

    Lugo, Joaquin N.; Smith, Gregory D.; Holley, Andrew J.

    2014-01-01

    In this experiment we present a technique to measure learning and memory. In the trace fear conditioning protocol presented here there are five pairings between a neutral stimulus and an unconditioned stimulus. There is a 20 sec trace period that separates each conditioning trial. On the following day freezing is measured during presentation of the conditioned stimulus (CS) and trace period. On the third day there is an 8 min test to measure contextual memory. The representative results are from mice that were presented with the aversive unconditioned stimulus (shock) compared to mice that received the tone presentations without the unconditioned stimulus. Trace fear conditioning has been successfully used to detect subtle learning and memory deficits and enhancements in mice that are not found with other fear conditioning methods. This type of fear conditioning is believed to be dependent upon connections between the medial prefrontal cortex and the hippocampus. One current controversy is whether this method is believed to be amygdala-independent. Therefore, other fear conditioning testing is needed to examine amygdala-dependent learning and memory effects, such as through the delay fear conditioning. PMID:24686718

  14. Idiotypic manipulation in mice: BALB/c mice can express the crossreactive idiotype of A/J mice.

    PubMed Central

    Moser, M; Leo, O; Hiernaux, J; Urbain, J

    1983-01-01

    The response of A/J mice to arsonate-coupled keyhole limpet hemocyanin is characterized by a crossreactive idiotype (CRIA). CRIA+ antibodies are restricted to the Igh-Ic haplotype and are never expressed in BALB/c mice after immunization with antigen. Studies at the DNA level suggest that the gene encoding the CRIA heavy chain in A/J mice is probably absent in the genome of BALB/c mice. Despite this, using the immunization cascade tool, we have been able to induce the expression of CRIA+ antibodies in BALB/c mice. These studies led to an apparent paradox, whose understanding will provide new insights into the regulatory mechanisms of the immune system. We suggest that clones secreting CRIA-like Igs in BALB/c mice are "somatic variants" that could arise from gene conversion events. PMID:6576348

  15. Characterization of metallothionein-I-transgenic mice.

    PubMed

    Iszard, M B; Liu, J; Liu, Y; Dalton, T; Andrews, G K; Palmiter, R D; Klaassen, C D

    1995-08-01

    A metallothionein-I-transgenic mouse strain (MT-TG) was characterized to determine whether they would be suitable to study the functions of this protein. MT-TG mice were visually indistinguishable from nontransgenic littermate controls, but had 10- to 20-fold higher basal levels of MT protein in pancreas, liver, and stomach, as well as 2- to 6-fold higher MT protein levels in other organs (kidney, intestine, uterus, testes, spleen, heart, and lung) than control mice, as determined by the Cd/hemoglobin assay. The MT-TG mice had 50% more Zn in liver and 300% more Zn in pancreas than control mice. Interestingly, female MT-TG mice have 4- to 5-fold higher MT levels in liver than those of males. To determine whether MT can be further increased by well-known MT inducers, control and MT-TG mice were given Zn (200 mumol/kg), Cd (20 mumol/kg), or diethyl maleate (DEM, 5 mmol/kg), and tissue MT concentrations were measured 24 hr later. MT-TG mice responded to MT inducers in a manner similar to control mice. The hepatic antioxidant components (glutathione (GSH), GSH-peroxidase, GSH-reductase, GSH S-transferase, superoxide dismutase, DT-diaphorase, and catalase) of MT-TG mice were not different from those of controls. The cytochrome P450 enzymes (total P450, b5, NADPH cytochrome c reductase) were normal in these MT-TG mice. The activities of CYP1A, CYP2B, and CYP2E enzymes in MT-TG mice were also similar to those of controls, as determined by ethoxy- and pentoxyresorufin O-dealkylation and chlorzoxazone 6-hydroxylation. Thus, MT-TG mice appear to be a good model for studying functions of MT. PMID:7645027

  16. The Gut Microbiota of Wild Mice

    PubMed Central

    Weldon, Laura; Abolins, Stephen; Lenzi, Luca; Bourne, Christian; Riley, Eleanor M.; Viney, Mark

    2015-01-01

    The gut microbiota profoundly affects the biology of its host. The composition of the microbiota is dynamic and is affected by both host genetic and many environmental effects. The gut microbiota of laboratory mice has been studied extensively, which has uncovered many of the effects that the microbiota can have. This work has also shown that the environments of different research institutions can affect the mouse microbiota. There has been relatively limited study of the microbiota of wild mice, but this has shown that it typically differs from that of laboratory mice (and that maintaining wild caught mice in the laboratory can quite quickly alter the microbiota). There is also inter-individual variation in the microbiota of wild mice, with this principally explained by geographical location. In this study we have characterised the gut (both the caecum and rectum) microbiota of wild caught Mus musculus domesticus at three UK sites and have investigated how the microbiota varies depending on host location and host characteristics. We find that the microbiota of these mice are generally consistent with those described from other wild mice. The rectal and caecal microbiotas of individual mice are generally more similar to each other, than they are to the microbiota of other individuals. We found significant differences in the diversity of the microbiotas among mice from different sample sites. There were significant correlations of microbiota diversity and body weight, a measure of age, body-mass index, serum concentration of leptin, and virus, nematode and mite infection. PMID:26258484

  17. Testosterone and Dihydrotestosterone Differentially Improve Cognition in Aged Female Mice

    ERIC Educational Resources Information Center

    Benice, Ted S.; Raber, Jacob

    2009-01-01

    Compared with age-matched male mice, female mice experience a more severe age-related cognitive decline (ACD). Since androgens are less abundant in aged female mice compared with aged male mice, androgen supplementation may enhance cognition in aged female mice. To test this, we assessed behavioral performance on a variety of tasks in 22- to

  18. Testosterone and Dihydrotestosterone Differentially Improve Cognition in Aged Female Mice

    ERIC Educational Resources Information Center

    Benice, Ted S.; Raber, Jacob

    2009-01-01

    Compared with age-matched male mice, female mice experience a more severe age-related cognitive decline (ACD). Since androgens are less abundant in aged female mice compared with aged male mice, androgen supplementation may enhance cognition in aged female mice. To test this, we assessed behavioral performance on a variety of tasks in 22- to…

  19. Mice cloned from skin cells.

    PubMed

    Li, Jinsong; Greco, Valentina; Guasch, Graldine; Fuchs, Elaine; Mombaerts, Peter

    2007-02-20

    Adult stem cells represent unique populations of undifferentiated cells with self-renewal capacity. In many tissues, stem cells divide less often than their progeny. It has been widely speculated, but largely untested, that their undifferentiated and quiescent state may make stem cells more efficient as donors for cloning by nuclear transfer (NT). Here, we report the use of nuclei from hair follicle stem cells and other skin keratinocytes as NT donors. When keratinocyte stem cells (KSCs) were used as NT donors, 19 liveborn mice were obtained, 9 of which survived to adulthood. Embryonic keratinocytes and cumulus cells also gave rise to cloned mice. Although cloning efficiencies were similar (<6% per transferred blastocyst), success rates were consistently higher for males than for females. Adult keratinocyte stem cells were better NT donors than so-called transit amplifying (TA) keratinocytes in both sexes (1.6% vs. 0% in females and 5.4% vs. 2.8% in males). Our findings reveal skin as a source of readily accessible stem cells, the nuclei of which can be reprogrammed to the pluripotent state by exposure to the cytoplasm of unfertilized oocytes. PMID:17299040

  20. Probabilistic numerical discrimination in mice.

    PubMed

    Berkay, Dilara; avdaro?lu, Bilgehan; Balc?, Fuat

    2016-03-01

    Previous studies showed that both human and non-human animals can discriminate between different quantities (i.e., time intervals, numerosities) with a limited level of precision due to their endogenous/representational uncertainty. In addition, other studies have shown that subjects can modulate their temporal categorization responses adaptively by incorporating information gathered regarding probabilistic contingencies into their time-based decisions. Despite the psychophysical similarities between the interval timing and nonverbal counting functions, the sensitivity of count-based decisions to probabilistic information remains an unanswered question. In the current study, we investigated whether exogenous probabilistic information can be integrated into numerosity-based judgments by mice. In the task employed in this study, reward was presented either after few (i.e., 10) or many (i.e., 20) lever presses, the last of which had to be emitted on the lever associated with the corresponding trial type. In order to investigate the effect of probabilistic information on performance in this task, we manipulated the relative frequency of different trial types across different experimental conditions. We evaluated the behavioral performance of the animals under models that differed in terms of their assumptions regarding the cost of responding (e.g., logarithmically increasingvs. no response cost). Our results showed for the first time that mice could adaptively modulate their count-based decisions based on the experienced probabilistic contingencies in directions predicted by optimality. PMID:26612627

  1. Teratogenicity of asbestos in mice.

    PubMed

    Fujitani, Tomoko; Hojo, Motoki; Inomata, Akiko; Ogata, Akio; Hirose, Akihiko; Nishimura, Tetsuji; Nakae, Dai

    2014-04-01

    Possible teratogenicity of 3 different asbestos (crocidolite, chrysotile and amosite) was assessed in CD1(ICR) mice. Dams on day 9 of gestation were given a single intraperitoneal administration at dose of 40 mg/kg body weight of asbestos suspended in 2% sodium carboxymethyl cellulose solution in phosphate buffered saline, while dams in the control group were given vehicle (10 ml/kg body weight). Dams and fetuses were examined on day 18 of gestation. To compare with the control group, the mean percentage of live fetuses in implantations in the group given crocidolite and the incidence of dams with early dead fetuses in the groups given chrysotile or amosite were increased. While no external or skeletal malformation was observed in the control group, the incidence of external malformation (mainly reduction deformity of limb) in the group given amosite, and the incidences of skeletal malformation (mainly fusion of vertebrae) in the all dosed groups were significantly increased. The result indicated that asbestos (crocidolite, chrysotile and amosite) have fetotoxicity and teratogenicity in mice. PMID:24646718

  2. MICE Spectrometer Magnet System Progress

    SciTech Connect

    Green, Michael A.; Virostek, Steve P.

    2007-08-27

    The first magnets for the muon ionization cooling experimentwill be the tracker solenoids that form the ends of the MICE coolingchannel. The primary purpose of the tracker solenoids is to provide auniform 4 T field (to better than +-0.3 percent over a volume that is 1meter long and 0.3 meters in diameter) spectrometer magnet field for thescintillating fiber detectors that are used to analyze the muons in thechannel before and after ionization cooling. A secondary purpose for thetracker magnet is the matching of the muon beam between the rest of theMICE cooling channel and the uniform field spectrometer magnet. Thetracker solenoid is powered by three 300 amp power supplies. Additionaltuning of the spectrometer is provided by a pair of 50 amp power suppliesacross the spectrometer magnet end coils. The tracker magnet will becooled using a pair of 4 K pulse tube coolers that each provide 1.5 W ofcooling at 4.2 K. Final design and construction of the tracker solenoidsbegan during the summer of 2006. This report describes the progress madeon the construction of the tracker solenoids.

  3. Euthanasia of neonatal mice with carbon dioxide

    USGS Publications Warehouse

    Pritchett, K.; Corrow, D.; Stockwell, J.; Smith, A.

    2005-01-01

    Exposure to carbon dioxide (CO2) is the most prevalent method used to euthanize rodents in biomedical research. The purpose of this study was to determine the time of CO2 exposure required to euthanize neonatal mice (0 to 10 days old). Multiple groups of mice were exposed to 100% CO 2 for time periods between 5 and 60 min. Mice were placed in room air for 10 or 20 min after CO2 exposure, to allow for the chance of recovery. If mice recovered at one time point, a longer exposure was examined. Inbred and outbred mice were compared. Results of the study indicated that time to death varied with the age of the animals and could be as long as 50 min on the day of birth and differed between inbred and outbred mice. Institutions euthanizing neonatal mice with CO2 may wish to adjust their CO 2 exposure time periods according the age of the mice and their genetic background. Copyright 2005 by the American Association for Laboratory Animal Science.

  4. The origin of SL family mice.

    PubMed

    Abujiang, P; Yamada, Y; Haller, O; Kobayashi, H; Kamoto, T; Lu, L M; Ogawa, M; Ishimoto, A; Katoh, H; Kanehira, K; Ikegami, S; Fukumoto, M; Hiai, H

    1996-08-01

    The origin of SL family mice was studied by analyzing 100 microsatellite loci, the major histocompatibility complex, the Mx gene, murine leukemia provirus, and mammary tumor provirus. From the genetic profile of family members and their history, we assumed the existence of a proto-SL mouse, an ancestor of all SL family members. Many alleles were contributed to the proto-SL by the ancestors related to strains A2G and CF#1, and/or some wild mice. Among four existing family members, SL/Am and SL/Ni mice were almost identical and presumably closest to the proto-SL. The SL/Kh mouse was derived from a cross of the proto-SL and AKR mice, because SL/Kh mice inherited a considerable number of genes from AKR mice, the most outstanding of which were those of the provirus Emv-11 and Thy-1.1. The SL/QDj mice seemed to be a recombinant inbred strain between SL/Am and SL/Kh mice, because their alleles at all 100 microsatellite loci were shared by SL/Am or SL/Kh strains or both. All four SL family members shared the major histocompatibility complex haplotype q. PMID:8872992

  5. Bacterial infections in Myd88-deficient mice.

    PubMed

    Villano, Jason S; Rong, Fang; Cooper, Timothy K

    2014-04-01

    Three breeding colonies of Myd88(-/-) mice had a history of significant morbidity and mortality. Although strain-specific poor reproductive performance might explain neonatal death and dystocia, mice were found dead or required euthanasia because of moribundity, distended abdomen, head tilt, and seizures. Histopathology results included bacteremia, placentitis, metritis, peritonitis with abscess formation, and suppurative meningoencephalitis. Intralesional gram-negative coccobacilli were present, often in extremely high number. Cultures of samples of the cardiac blood of a mouse and from water-bottle sipper tubes provided to some affected mice grew Pseudomonas aeruginosa. In addition, affected tissues from 2 mice and feces from a third tested PCR-positive for P. aeruginosa. Although the mice had received autoclaved reverse-osmosis-purified drinking water, we suspect that the mice were inoculated with P. aeruginosa through contaminated sipper tubes. Because of the deficiency in most of the Toll-like receptor signaling pathways, these Myd88(-/-) mice were unlikely to have developed competitive innate and adaptive immune responses, resulting in bacterial infections. These clinical cases underscore the importance of understanding how genotype, phenotype and environment affect animal health. Sound husbandry and experimental practices are needed to prevent the exposure of immuno-deficient mice to pathogens. PMID:24674585

  6. Hyperaldosteronism in Klotho-deficient mice.

    PubMed

    Fischer, Stephanie S; Kempe, Daniela S; Leibrock, Christina B; Rexhepaj, Rexhep; Siraskar, Balasaheb; Boini, Krishna M; Ackermann, Teresa F; Fller, Michael; Hocher, Berthold; Rosenblatt, Kevin P; Kuro-O, Makoto; Lang, Florian

    2010-11-01

    Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25-dihydroxyvitamin-D(3) [1,25(OH)(2)D(3)]. It participates in the regulation of renal tubular phosphate reabsorption and stimulates renal tubular Ca(2+) reabsorption. Klotho hypomorphic mice (klotho(hm)) suffer from severe growth deficit, rapid aging, and early death, events largely reversed by a vitamin D-deficient diet. The present study explored the role of Klotho deficiency in mineral and electrolyte metabolism. To this end, klotho(hm) mice and wild-type mice (klotho(+/+)) were subjected to a normal (D(+)) or vitamin D-deficient (D(-)) diet or to a vitamin D-deficient diet for 4 wk and then to a normal diet (D(-/+)). At the age of 8 wk, body weight was significantly lower in klotho(hm)D(+) mice than in klotho(+/+)D(+) mice, klotho(hm)D(-) mice, and klotho(hm)D(-/+) mice. Plasma concentrations of 1,25(OH)(2)D(3,) adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), and aldosterone were significantly higher in klotho(hm)D(+) mice than in klotho(+/+)D(+) mice. Plasma volume was significantly smaller in klotho(hm)D(-/+) mice, and plasma urea, Ca(2+), phosphate and Na(+), but not K(+) concentrations were significantly higher in klotho(hm)D(+) mice than in klotho(+/+)D(+) mice. The differences were partially abrogated by a vitamin D-deficient diet. Moreover, the hyperaldosteronism was partially reversed by Ca(2+)-deficient diet. Ussing chamber experiments revealed a marked increase in amiloride-sensitive current across the colonic epithelium, pointing to enhanced epithelial sodium channel (ENaC) activity. A salt-deficient diet tended to decrease and a salt-rich diet significantly increased the life span of klotho(hm)D(+) mice. In conclusion, the present observation disclose that the excessive formation of 1,25(OH)(2)D(3) in Klotho-deficient mice results in extracellular volume depletion, which significantly contributes to the shortening of life span. PMID:20719979

  7. Video-oculography in Mice

    PubMed Central

    de Jeu, Marcel; De Zeeuw, Chris I.

    2012-01-01

    Eye movements are very important in order to track an object or to stabilize an image on the retina during movement. Animals without a fovea, such as the mouse, have a limited capacity to lock their eyes onto a target. In contrast to these target directed eye movements, compensatory ocular eye movements are easily elicited in afoveate animals1,2,3,4. Compensatory ocular movements are generated by processing vestibular and optokinetic information into a command signal that will drive the eye muscles. The processing of the vestibular and optokinetic information can be investigated separately and together, allowing the specification of a deficit in the oculomotor system. The oculomotor system can be tested by evoking an optokinetic reflex (OKR), vestibulo-ocular reflex (VOR) or a visually-enhanced vestibulo-ocular reflex (VVOR). The OKR is a reflex movement that compensates for "full-field" image movements on the retina, whereas the VOR is a reflex eye movement that compensates head movements. The VVOR is a reflex eye movement that uses both vestibular as well as optokinetic information to make the appropriate compensation. The cerebellum monitors and is able to adjust these compensatory eye movements. Therefore, oculography is a very powerful tool to investigate brain-behavior relationship under normal as well as under pathological conditions (f.e. of vestibular, ocular and/or cerebellar origin). Testing the oculomotor system, as a behavioral paradigm, is interesting for several reasons. First, the oculomotor system is a well understood neural system5. Second, the oculomotor system is relative simple6; the amount of possible eye movement is limited by its ball-in-socket architecture ("single joint") and the three pairs of extra-ocular muscles7. Third, the behavioral output and sensory input can easily be measured, which makes this a highly accessible system for quantitative analysis8. Many behavioral tests lack this high level of quantitative power. And finally, both performance as well as plasticity of the oculomotor system can be tested, allowing research on learning and memory processes9. Genetically modified mice are nowadays widely available and they form an important source for the exploration of brain functions at various levels10. In addition, they can be used as models to mimic human diseases. Applying oculography on normal, pharmacologically-treated or genetically modified mice is a powerful research tool to explore the underlying physiology of motor behaviors under normal and pathological conditions. Here, we describe how to measure video-oculography in mice8. PMID:22847328

  8. Video-oculography in mice.

    PubMed

    de Jeu, Marcel; De Zeeuw, Chris I

    2012-01-01

    Eye movements are very important in order to track an object or to stabilize an image on the retina during movement. Animals without a fovea, such as the mouse, have a limited capacity to lock their eyes onto a target. In contrast to these target directed eye movements, compensatory ocular eye movements are easily elicited in afoveate animals. Compensatory ocular movements are generated by processing vestibular and optokinetic information into a command signal that will drive the eye muscles. The processing of the vestibular and optokinetic information can be investigated separately and together, allowing the specification of a deficit in the oculomotor system. The oculomotor system can be tested by evoking an optokinetic reflex (OKR), vestibulo-ocular reflex (VOR) or a visually-enhanced vestibulo-ocular reflex (VVOR). The OKR is a reflex movement that compensates for "full-field" image movements on the retina, whereas the VOR is a reflex eye movement that compensates head movements. The VVOR is a reflex eye movement that uses both vestibular as well as optokinetic information to make the appropriate compensation. The cerebellum monitors and is able to adjust these compensatory eye movements. Therefore, oculography is a very powerful tool to investigate brain-behavior relationship under normal as well as under pathological conditions (f.e. of vestibular, ocular and/or cerebellar origin). Testing the oculomotor system, as a behavioral paradigm, is interesting for several reasons. First, the oculomotor system is a well understood neural system. Second, the oculomotor system is relative simple; the amount of possible eye movement is limited by its ball-in-socket architecture ("single joint") and the three pairs of extra-ocular muscles. Third, the behavioral output and sensory input can easily be measured, which makes this a highly accessible system for quantitative analysis. Many behavioral tests lack this high level of quantitative power. And finally, both performance as well as plasticity of the oculomotor system can be tested, allowing research on learning and memory processes. Genetically modified mice are nowadays widely available and they form an important source for the exploration of brain functions at various levels. In addition, they can be used as models to mimic human diseases. Applying oculography on normal, pharmacologically-treated or genetically modified mice is a powerful research tool to explore the underlying physiology of motor behaviors under normal and pathological conditions. Here, we describe how to measure video-oculography in mice. PMID:22847328

  9. Pion contamination in the MICE muon beam

    NASA Astrophysics Data System (ADS)

    Adams, D.; Alekou, A.; Apollonio, M.; Asfandiyarov, R.; Barber, G.; Barclay, P.; de Bari, A.; Bayes, R.; Bayliss, V.; Bertoni, R.; Blackmore, V. J.; Blondel, A.; Blot, S.; Bogomilov, M.; Bonesini, M.; Booth, C. N.; Bowring, D.; Boyd, S.; Brashaw, T. W.; Bravar, U.; Bross, A. D.; Capponi, M.; Carlisle, T.; Cecchet, G.; Charnley, C.; Chignoli, F.; Cline, D.; Cobb, J. H.; Colling, G.; Collomb, N.; Coney, L.; Cooke, P.; Courthold, M.; Cremaldi, L. M.; DeMello, A.; Dick, A.; Dobbs, A.; Dornan, P.; Drews, M.; Drielsma, F.; Filthaut, F.; Fitzpatrick, T.; Franchini, P.; Francis, V.; Fry, L.; Gallagher, A.; Gamet, R.; Gardener, R.; Gourlay, S.; Grant, A.; Greis, J. R.; Griffiths, S.; Hanlet, P.; Hansen, O. M.; Hanson, G. G.; Hart, T. L.; Hartnett, T.; Hayler, T.; Heidt, C.; Hills, M.; Hodgson, P.; Hunt, C.; Iaciofano, A.; Ishimoto, S.; Kafka, G.; Kaplan, D. M.; Karadzhov, Y.; Kim, Y. K.; Kuno, Y.; Kyberd, P.; Lagrange, J.-B.; Langlands, J.; Lau, W.; Leonova, M.; Li, D.; Lintern, A.; Littlefield, M.; Long, K.; Luo, T.; Macwaters, C.; Martlew, B.; Martyniak, J.; Mazza, R.; Middleton, S.; Moretti, A.; Moss, A.; Muir, A.; Mullacrane, I.; Nebrensky, J. J.; Neuffer, D.; Nichols, A.; Nicholson, R.; Nugent, J. C.; Oates, A.; Onel, Y.; Orestano, D.; Overton, E.; Owens, P.; Palladino, V.; Pasternak, J.; Pastore, F.; Pidcott, C.; Popovic, M.; Preece, R.; Prestemon, S.; Rajaram, D.; Ramberger, S.; Rayner, M. A.; Ricciardi, S.; Roberts, T. J.; Robinson, M.; Rogers, C.; Ronald, K.; Rubinov, P.; Rucinski, P.; Sakamato, H.; Sanders, D. A.; Santos, E.; Savidge, T.; Smith, P. J.; Snopok, P.; Soler, F. J. P.; Speirs, D.; Stanley, T.; Stokes, G.; Summers, D. J.; Tarrant, J.; Taylor, I.; Tortora, L.; Torun, Y.; Tsenov, R.; Tunnell, C. D.; Uchida, M. A.; Vankova-Kirilova, G.; Virostek, S.; Vretenar, M.; Warburton, P.; Watson, S.; White, C.; Whyte, C. G.; Wilson, A.; Winter, M.; Yang, X.; Young, A.; Zisman, M.

    2016-03-01

    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240 MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than ~1% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is fπ < 1.4% at 90% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.

  10. Endurance exercise training in myostatin null mice.

    PubMed

    Savage, Kathleen J; McPherron, Alexandra C

    2010-09-01

    The growth factor myostatin (Mstn) is a negative regulator of skeletal muscle mass. Mstn(-/-) muscles are hypertrophied, stronger, and more glycolytic than Mstn(+/+) muscles, suggesting that they might not perform endurance exercise as well as Mstn(+/+) mice. Indeed, it has previously been shown that treadmill exercise training reduces triceps weight in Mstn(-/-) mice. To analyze the response of Mstn(-/-) muscle to endurance exercise in detail, we carried out endurance training over 4 weeks to examine muscle mass, histology, and oxidative enzyme activity. We found that muscle mass was reduced with training in several muscles from both genotypes, with no evidence of muscle damage. Citrate synthase activity was increased with training in control and mutant mice. Non-trained Mstn(-/-) mice did, however, have lower maximal exercise capacity compared with Mstn(+/+) mice. These results show that Mstn(-/-) muscle retains the metabolic plasticity necessary to adapt normally to endurance training. PMID:20544938

  11. Infectious diseases in humanized mice.

    PubMed

    Leung, Carol; Chijioke, Obinna; Gujer, Cornelia; Chatterjee, Bithi; Antsiferova, Olga; Landtwing, Vanessa; McHugh, Donal; Raykova, Ana; Münz, Christian

    2013-09-01

    Despite many theoretical incompatibilities between mouse and human cells, mice with reconstituted human immune system components contain nearly all human leukocyte populations. Accordingly, several human-tropic pathogens have been investigated in these in vivo models of the human immune system, including viruses such as human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV), as well as bacteria such as Mycobacterium tuberculosis and Salmonella enterica Typhi. While these studies initially aimed to establish similarities in the pathogenesis of infections between these models and the pathobiology in patients, recent investigations have provided new and interesting functional insights into the protective value of certain immune compartments and altered pathology upon mutant pathogen infections. As more tools and methodologies are developed to make these models more versatile to study human immune responses in vivo, such improvements build toward small animal models with human immune components, which could predict immune responses to therapies and vaccination in human patients. PMID:23913412

  12. Assessing delay discounting in mice

    PubMed Central

    Mitchell, Suzanne H.

    2014-01-01

    Delay discounting (also intertemporal choice or impulsive choice) is the process by which delayed outcomes, such as delayed food delivery, are valued less than the same outcomes delivered immediately or with a shorter delay. This process is of interest because many psychopathologies, including substance dependence, pathological gambling, attention deficit hyperactivity disorder and conduct disorder, are characterized by heightened levels of delay discounting. Some of these disorders are heritable, and data indicate that delay discounting also has a genetic component. To identify the genes underlying the delay discounting decision-making process and genetic correlates of heightened discounting, researchers have used mouse models. This unit describes a protocol for generating delay discounting behavior in mice and discusses analysis techniques for such behavior. PMID:24510779

  13. Phenotyping Circadian Rhythms in Mice

    PubMed Central

    Eckel-Mahan, Kristin; Sassone-Corsi, Paolo

    2015-01-01

    Circadian rhythms take place with a periodicity of twenty-four hours, temporally following the rotation of the earth around its axis. Examples of circadian rhythms are the sleep/wake cycle, feeding, and hormone secretion. Light powerfully entrains the mammalian clock and assists in keeping animals synchronized to the 24-hour cycle of the earth by activating specific neurons in the “central pacemaker” of the brain, the suprachiasmatic nucleus. Absolute periodicity of an animal can deviate slightly from 24 hours as manifest when an animal is placed into constant dark- or “free running”- conditions. Simple measurements of an organism's activity in free running conditions reveal its intrinsic circadian period. Mice are a particularly useful model for studying circadian rhythmicity due to the ease of genetic manipulation, thus identifying molecular contributors to rhythmicity. Furthermore, their small size allows for monitoring locomotion or activity in their home cage environment with relative ease. Several tasks commonly used to analyze circadian periodicity and plasticity in mice are outlined here including the process of entrainment, determination of tau (period length) in free running conditions, determination of circadian periodicity in response to light disruption (i.e. jet lag studies), and evaluation of clock plasticity in non-twenty-four hour conditions (T-cycles). Studying the properties of circadian periods such as their phase, amplitude, and length in response to photic perturbation, can be particularly useful in understanding how humans respond to jet lag, night shifts, rotating shifts, or other transient or chronic disruption of one's environmental surroundings. PMID:26331760

  14. Experimental anisakid infections in mice.

    PubMed

    Vericimo, M A; Figueiredo, I; Teixeira, G A P B; Clemente, S C São

    2015-09-01

    Anisakidosis is a human parasitic disease caused by infections with members of the Anisakidae family. Accidental infection after fish intake affects the gastrointestinal tract as a consequence of mechanical damage caused by migrating larvae. Infections can also trigger allergies, hives, severe asthma or anaphylaxis with angioedema. Although mouse models of intraperitoneal antigenic stimulation exist, enabling immunological studies, few models using gastric introduction of live larvae are available for the study of immunological and gastrointestinal damage in mice. This study was designed to characterize serum reactivity against Anisakis spp. and Contracaecum spp. in Balb/c mice following orogastric inoculation and to assess gastrointestinal damage. These anisakid species were classified at the Universidade Federal Fluminense (UFF) School of Veterinary Medicine and materials for live larval inoculation were developed at the UFF Immunobiology laboratory. Live larvae were inoculated following injection with a NaCl solution. Blood samples were collected and sera screened for immunoglobulin (Ig)E and IgG anti-larva responses to both nematodes, specific for somatic and excretory/secretory antigens, by enzyme-linked immunosorbent assay (ELISA). The means of the optical densities were analysed using analysis of variance (ANOVA) with Tukey's post-hoc test and the general linear model. This analysis identified the presence of anti-IgG seroreactivity to both somatic and excretory/secretory Anisakis antigens in inoculated animals compared with controls (P< 0.001), and no gastric or intestinal damage was observed. These experiments demonstrated that introduction of live Contracaecum spp. into the gastrointestinal tract did not elicit serum sensitization in animals. PMID:24780178

  15. Social reward among juvenile mice

    PubMed Central

    Panksepp, J B; Lahvis, G P

    2007-01-01

    Mammalian social relationships, such as mother–offspring attachments and pair bonds, can directly affect reproductive output. However, conspecifics approach one another in a comparatively broad range of contexts, so conceivably there are motivations for social congregation other than those underlying reproduction, parental care or territoriality. Here, we show that reward mediated by social contact is a fundamental aspect of juvenile mouse sociality. Employing a novel social conditioned place preference (SCPP) procedure, we demonstrate that social proximity is rewarding for juvenile mice from three inbred strains (A/J, C57BL/6J and DBA/2J), while mice from a fourth strain (BALB/cJ) are much less responsive to social contact. Importantly, this strain-dependent difference was not related to phenotypic variability in exploratory behavior or contextual learning nor influenced by the genetic background associated with maternal care or social conditioning. Furthermore, the SCPP phenotype was expressed early in development (postnatal day 25) and did not require a specific sex composition within the conditioning group. Finally, SCPP responses resulted from an interaction between two specifiable processes: one component of the interaction facilitated approach toward environments that were associated with social salience, whereas a second component mediated avoidance of environmental cues that predicted social isolation. We have thus identified a genetically prescribed process that can attribute value onto conditions predicting a general form of social contact. To our knowledge, this is the first definitive evidence to show that genetic variation can influence a form of social valuation not directly related to a reproductive behavior. PMID:17212648

  16. Obesity impairs wound healing in ovariectomized female mice.

    PubMed

    Holcomb, Valerie B; Keck, Victoria A; Barrett, J Carl; Hong, Jina; Libutti, Steven K; Nunez, Nomeli P

    2009-01-01

    Obesity is increasing worldwide. Estrogen protects female mice from gaining weight in contrast to ovariectomy. Excess weight can inhibit wound healing. We determine the effects of obesity on wound healing in the presence and absence of estrogen. For this purpose, we generated (ovariectomized (OVX) and non-ovariectomized (NOVX)) lean mice by feeding a 30% calorie-restricted diet (CR), overweight mice a low-fat (LF) diet and obese mice a high-fat (HF) diet. CR mice had the lowest, LF an intermediate, and HF mice the highest body weights. OVX exacerbated weight gain in female mice. Wounds healed fastest in CR mice regardless of estrogen status. Contrastingly, wound healing in OVX obese female mice was delayed. In sum, OVX increased the propensity of gaining weight, CR mice healed wounds more rapidly than obese mice irrespective of estrogen status, and obesity in the absence of estrogen impaired wound healing. PMID:19567384

  17. Behavioral analysis of relaxin-3 deficient mice.

    PubMed

    Tanaka, Masaki; Furube, Eriko; Aoki, Miku; Watanabe, Yoshihisa

    2013-01-01

    Relaxin-3 is a neuropeptide belonging to the relaxin/insulin superfamily. Studies using rodents have revealed that relaxin-3 is predominantly expressed in neurons in the nucleus incertus of the pons, projecting axons to forebrain regions including the hypothalamus. There is evidence that relaxin-3 is involved in several functions, including food intake and stress responses. We generated relaxin-3 gene knockout (KO) mice and examined them using a battery of behavioral tests of sensory/motor functions and emotion-related behaviors. Relaxin-3 KO mice exhibited normal growth and appearance. There was no difference in bodyweight among genotypes in both normal and high fat diet feeding. In addition, there were no significant differences between wild-type and KO mice in social interaction, depression-like behavior, and short memory test. However, in the elevated plus maze test, KO mice exhibited a robust increase in the tendency to enter open arms, although they exhibited normal performance in a light/dark transition test and showed no difference from wild-type mice in the open field test. Taken together, these results indicate that relaxin-3 KO mice exhibit mild anxiolytic characteristics relative to wild-type mice, suggesting that this peptide is involved in anxiety-related behavior. PMID:24640573

  18. Pulmonary infection of mice with Staphylococcus aureus.

    PubMed

    DeMaria, T F; Kapral, F A

    1978-07-01

    The survival of Staphylococcus aureus in the lungs of mice was studied under various conditions. Doses of 10(7) to 10(9) washed staphylococci were quantitatively introduced into the lungs after intratracheal inoculation in mice under either ether or sodium pentobarbital anesthesia. Mice were sacrificed at intervals, the lungs were excised and homogenized, and the cocci were enumerated by plate count. The 50% lethal dose was 6 x 10(8) cocci per mouse, and mice died within 24 h but without proliferation of the inoculum. Mice given 10(8) cocci intratracheally under pentobarbital anesthesia regularly survived and eliminated the organisms over a 48-h period. The use of ether anesthesia resulted in persistence of the inoculum for up to 48 h, but the organisms were then eliminated. Inability to proliferate did not appear to result from a lack of iron because pretreatment of the mice with ferric ammonium citrate or Imferon did not alter inoculum survival. Staphylococci inoculated intratracheally in mice infected with influenza virus 3 to 21 days previously showed no enhanced persistence or multiplication. Cocci preclumped with fibrinogen, inocula mixed with 10 times the number of Formalin-killed staphylococci, or inocula of the encapsulated Smith strain did not survive any better than conventional inocula, suggesting that phagocytosis might not be the sole mechanism for elimination. However, a sedimentable fraction from normal or infected lung homogenates proved either inhibitory or cidal for staphylococci in vitro. PMID:711310

  19. Lethality In Mice Following Localized Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Ferrario, Angela; Gomer, Charles J.; Murphree, A. L.

    1989-06-01

    Porphyrin photodynamic therapy directed specifically to the hind leg of various strains of mice was found to induce a high percentage of lethality at dosages which would be required to achieve cures in tumor bearing mice. Toxicity was observed in both pigmented and albino mouse strains. An inverse relationship between light dose rate and lethality was documented. Anti-coagulant drugs and anti-inflammatory agents which inhibit cyclo-oxygenase had protective effects. The response induced by localized PDT appears to mimic that of a classical traumatic shock syndrome and may be limited to PDT in small animals such as mice.

  20. Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice.

    PubMed Central

    Hrelia, P; Maffei, F; Vigagni, F; Fimognari, C; Flori, P; Stanzani, R; Cantelli Forti, G

    1994-01-01

    A combined cytogeneticurine metabolite analysis approach was used to assess potential interactive effects between Fenarimol (FN), a fungicide, and trichloroethylene (TRI), a halogenated solvent. FN was demonstrated to selectively induce P450-2B1 isoforms in different organs of treated mice. Since the rate of metabolism and the stereospecificity of metabolism are dependent on the types and amount of P450s available, FN might drastically alter the metabolic activation of a precarcinogen, such as TRI, and its toxicological consequences. Male CD1 mice were divided into untreated, vehicle control, and experimental groups. Animals of the latter groups were treated ip with 150 mg/kg bw FN in corn oil, 457 mg/kg bw TRI in corn oil, TRI plus FN separated by different time intervals. Bone marrow cells were harvested for determination of micronuclei (MN) frequencies in polychromatic erythrocytes (PCE). The presence of the known metabolite of TRI, trichloroethanol (TCE), was quantitated in collected urine by gas chromatography using an electron-capture detector. Linear regression analysis shows that MN frequency by TRI is correlated with TCE concentration in urine. Observed potentiation of genotoxicity of TRI by FN pretreatment (1 hr before TRI treatment) apparently reflects changes in the spectra of enzymes involved in TRI metabolism, and altered toxicokinetic, as witnessed by the 20% difference in TCE excretion from combined treated mice. However, no increased genetic or metabolic effects were observed when FN was administered 3 hr before TRI. No significant interactive effects were observed at a genetic level when FN was administered 1 hr and 3 hr after TRI whereas a 33 to 47% loss in TCE excretion was recorded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7698080

  1. Genetically modified mice models for Alzheimer's disease.

    PubMed

    Sankaranarayanan, Sethu

    2006-01-01

    Transgenic mice models for Alzheimer's disease (AD) are essential to the understanding of disease pathophysiology, develop robust behavioral models and predict outcomes from pharmacological interventions. In the last 10 years, numerous mice models have been developed particularly focusing on the amyloid precursor protein-processing pathway and Tau pathology since brain amyloid deposits and Tau tangles are some of the primary neuropathological consequences of AD. Current views on the amyloid hypothesis and mice models relating to the role of soluble Abeta oligomers and intracellular Abeta in AD pathophysiology will be reviewed. Several novel transgenic mice models that have recently been developed and their potential impact on understanding disease pathogenesis will also be summarized. PMID:16712495

  2. The Olfactory Transcriptomes of Mice

    PubMed Central

    Ibarra-Soria, Ximena; Levitin, Maria O.; Saraiva, Luis R.; Logan, Darren W.

    2014-01-01

    The olfactory (OR) and vomeronasal receptor (VR) repertoires are collectively encoded by 1700 genes and pseudogenes in the mouse genome. Most OR and VR genes were identified by comparative genomic techniques and therefore, in many of those cases, only their protein coding sequences are defined. Some also lack experimental support, due in part to the similarity between them and their monogenic, cell-specific expression in olfactory tissues. Here we use deep RNA sequencing, expression microarray and quantitative RT-PCR in both the vomeronasal organ and whole olfactory mucosa to quantify their full transcriptomes in multiple male and female mice. We find evidence of expression for all VR, and almost all OR genes that are annotated as functional in the reference genome, and use the data to generate over 1100 new, multi-exonic, significantly extended receptor gene annotations. We find that OR and VR genes are neither equally nor randomly expressed, but have reproducible distributions of abundance in both tissues. The olfactory transcriptomes are only minimally different between males and females, suggesting altered gene expression at the periphery is unlikely to underpin the striking sexual dimorphism in olfactory-mediated behavior. Finally, we present evidence that hundreds of novel, putatively protein-coding genes are expressed in these highly specialized olfactory tissues, and carry out a proof-of-principle validation. Taken together, these data provide a comprehensive, quantitative catalog of the genes that mediate olfactory perception and pheromone-evoked behavior at the periphery. PMID:25187969

  3. Intravenous Injections in Neonatal Mice

    PubMed Central

    Gombash Lampe, Sara E.; Kaspar, Brian K.; Foust, Kevin D.

    2014-01-01

    Intravenous injection is a clinically applicable manner to deliver therapeutics. For adult rodents and larger animals, intravenous injections are technically feasible and routine. However, some mouse models can have early onset of disease with a rapid progression that makes administration of potential therapies difficult. The temporal (or facial) vein is just anterior to the ear bud in mice and is clearly visible for the first two days after birth on either side of the head using a dissecting microscope. During this window, the temporal vein can be injected with volumes up to 50 μl. The injection is safe and well tolerated by both the pups and the dams. A typical injection procedure is completed within 1-2 min, after which the pup is returned to the home cage. By the third postnatal day the vein is difficult to visualize and the injection procedure becomes technically unreliable. This technique has been used for delivery of adeno-associated virus (AAV) vectors, which in turn can provide almost body-wide, stable transgene expression for the life of the animal depending on the viral serotype chosen. PMID:25407048

  4. Measuring local anaphylaxis in mice.

    PubMed

    Evans, Holly; Killoran, Kristin E; Mitre, Edward

    2014-01-01

    Allergic responses are the result of the activation of mast cells and basophils, and the subsequent release of vasoactive and proinflammatory mediators. Exposure to an allergen in a sensitized individual can result in clinical symptoms that vary from minor erythema to life threatening anaphylaxis. In the laboratory, various animal models have been developed to understand the mechanisms driving allergic responses. Herein, we describe a detailed method for measuring changes in vascular permeability to quantify localized allergic responses. The local anaphylaxis assay was first reported in the 1920s, and has been adapted from the technique published by Kojima et al. in 2007(1). In this assay, mice sensitized to OVA are challenged in the left ear with vehicle and in the right ear with OVA. This is followed by an intravenous injection of Evans Blue dye. Ten min after injecting Evans Blue, the animal is euthanized and the dye that has extravasated into the ears is extracted overnight in formamide. The absorbance of the extracted dye is then quantified with a spectrophotometer. This method reliably results in a visual and quantifiable manifestation of a local allergic response. PMID:25350839

  5. Cytochrome P450 humanised mice

    PubMed Central

    2004-01-01

    Humans are exposed to countless foreign compounds, typically referred to as xenobiotics. These can include clinically used drugs, environmental pollutants, food additives, pesticides, herbicides and even natural plant compounds. Xenobiotics are metabolised primarily in the liver, but also in the gut and other organs, to derivatives that are more easily eliminated from the body. In some cases, however, a compound is converted to an electrophile that can cause cell toxicity and transformation leading to cancer. Among the most important xenobiotic-metabolising enzymes are the cytochromes P450 (P450s). These enzymes represent a superfamily of multiple forms that exhibit marked species differences in their expression and catalytic activities. To predict how humans will metabolise xenobiotics, including drugs, human liver extracts and recombinant P450s have been used. New humanised mouse models are being developed which will be of great value in the study of drug metabolism, pharmacokinetics and pharmacodynamics in vivo, and in carrying out human risk assessment of xenobiotics. Humanised mice expressing CYP2D6 and CYP3A4, two major drug-metabolising P450s, have revealed the feasibility of this approach. PMID:15588489

  6. Of Mice and Men: Experimental Induction of Calcium Oxalate Nephrolithiasis in Mice

    PubMed Central

    Khan, Saeed R.; Glenton, Patricia A.

    2013-01-01

    Purpose Availability of various transgenic and knockout mice provides an excellent opportunity to better understand the pathophysiology of calcium oxalate (CaOx) stone disease. However attempts to produce CaOx nephrolithiasis in mice have not been very successful. We have hypothesized that CaOx nephrolithiasis in mice requires increasing the urinary excretion of calcium as well as oxalate and that experimentally induced hyperoxaluria alone is not sufficient. To provide evidence we induced hyperoxaluria by administering hyperoxaluria inducing agents to normocalciuric as well as hypercalciuric mice and investigated various aspects of nephrolithiasis. Materials and Methods Ethylene glycol (EG), glyoxylate (GOx) or hydroxyl proline (HLP) were administered through diet to male and female normocalciuric B6 mice as well as hypercalciuric Npt2a −/− mice for 4 weeks. 24 hour urine samples were collected on 0.3,7,14,21 and 28 days and analyzed for pH, creatinine, lactate dehydrogensae (LDH) calcium and oxalate. Kidneys were examined using light microscopy. Urine was examined for crystals using both light and scanning electron microscopy. Results Hypercalciuric mice on HLP did not tolerate the treatment and had to be sacrificed before 28 days. All mice receiving EG, GOx or HLP became hyperoxaluric and demonstrated CaOx crystalluria. None of the female mice, normo or hypercalciuric developed renal CaOx crystal deposits. All mice on Gox and some on EG developed CaOx nephrolithiais. Kidneys of all mice showed epithelial injury. Male mice particularly on GOx showed more renal injury and migration of inflammatory cells into the interstitium around the crystal deposits. Conclusions Results confirm that induction of hyperoxaluria alone is not sufficient for CaOx nephrolithiais in mice. Hypercalciuria is also required. Kidneys of male mice are more prone to injury than those of female mice and are susceptible to CaOx crystal deposition. Perhaps epithelial injury promotes crystal retention. Thus CaOx nephrolithiais in mice is gender dependent and requires both hypercalciuria and hyperoxaluria. PMID:20663521

  7. Pharmacological aspects of metaldehyde poisoning in mice.

    PubMed

    Homeida, A M; Cooke, R G

    1982-03-01

    Metaldehyde, when administered orally to mice at a dose of 1 g kg-1, produced convulsions and death within 2 h. Brain concentrations of noradrenaline (NA) 5-hydroxytryptamie (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly reduced in these animals relative to controls. Treatment with either intraperitoneal clonidine or diazepam 20 min after administration of metaldehyde reduced the mortality rate and in mice surviving for 5 h, the decrease in brain NA and 5-HT concentrations were significantly reduced. PMID:6178838

  8. Normal Conducting RF Cavity for MICE

    SciTech Connect

    Li, D.; DeMello, A.; Virostek, S.; Zisman, M.; Summers, D.

    2010-05-23

    Normal conducting RF cavities must be used for the cooling section of the international Muon Ionization Cooling Experiment (MICE), currently under construction at Rutherford Appleton Laboratory (RAL) in the UK. Eight 201-MHz cavities are needed for the MICE cooling section; fabrication of the first five cavities is complete. We report the cavity fabrication status including cavity design, fabrication techniques and preliminary low power RF measurements.

  9. No evidence of cross-reactivity of human antibodies to a 33-mer peptide of the alpha-gliadin component of gluten with Bordetella pertussis pertactin.

    PubMed

    He, Qiushui; Viljanen, Matti K; Hinkkanen, Ari E; Arvilommi, Heikki; Mertsola, Jussi; Viander, Markku

    2005-05-01

    A 33-mer peptide of the alpha-gliadin component of gluten was recently identified as primary initiator of the inflammatory response to gluten in coeliac disease (CD) patients. This proline-glutamine-rich peptide (PG-peptide) is highly homologous to internal sequence of pertactin, an immunogenic protein of Bordetella pertussis. Using enzyme immunoassays, we measured serum antibodies to pertactin and to PG-peptide in 167 Finnish subjects including pertussis vaccine recipients and pertussis patients, CD and non-CD patients and healthy individuals. We found no cross-reactivity between human antibodies to the two different components, suggesting that neither pertussis immunization nor disease contributes to the pathogenesis of CD. PMID:15837240

  10. Diagnosis of cardiac metastasis from cervical cancer in a 33-year-old patient using multimodal imaging studies: a case report and literature review

    PubMed Central

    Hoksch, Beatrix; Schwerzmann, Markus; Puig, Stefan; Klink, Thorsten

    2014-01-01

    We report a case of a 33-year-old woman with emergency admission due to dyspnoea and fever. History included squamous cell carcinoma of the cervix in complete remission. Contrast-enhanced computed tomography (CT) scanning of the chest, which was indicated to rule out pneumonia, revealed an infiltrative cardiac mass. Further assessment of the tumour by echocardiography and cardiac magnetic resonance imaging (MRI) showed transmural infiltration of the apical interventricular septum with a mass extending into the left and right ventricle cavities. The mass was highly suspicious for a cardiac metastasis. Cardiac metastases from cervical cancer are extremely rare. Recurrence of cervical carcinoma involving the heart should be considered even after a curative therapy approach. Non-invasive imaging plays a paramount role in investigating cardiac masses. Echocardiography, CT and MRI are complementary imaging modalities for complete work-up of intracardiac lesions. PMID:25346849

  11. Palmoplantar keratoderma in Slurp2-deficient mice

    PubMed Central

    Allan, Christopher M.; Procaccia, Shiri; Tran, Deanna; Tu, Yiping; Barnes, Richard H.; Larsson, Mikael; Allan, Bernard B.; Young, Lorraine C.; Hong, Cynthia; Tontonoz, Peter; Fong, Loren G.; Young, Stephen G.; Beigneux, Anne P.

    2015-01-01

    SLURP1, a member of the Ly6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Another secreted Ly6 protein, SLURP2, is encoded by a gene located ~20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2–3 sequences had been replaced with lacZ and neo cassettes. Slurp2−/− mice exhibited hyperkeratosis on the volar surface of the paws (i.e., PPK), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are very similar to those of Slurp1−/− mice. To solidify a link between Slurp2 deficiency and PPK and to be confident that the disease phenotypes in Slurp2−/− mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X−/−) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X−/− mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes. PMID:26967477

  12. Hypothyroidism compromises hypothalamic leptin signaling in mice.

    PubMed

    Groba, Claudia; Mayerl, Steffen; van Mullem, Alies A; Visser, Theo J; Darras, Veerle M; Habenicht, Andreas J; Heuer, Heike

    2013-04-01

    The impact of thyroid hormone (TH) on metabolism and energy expenditure is well established, but the role of TH in regulating nutritional sensing, particularly in the central nervous system, is only poorly defined. Here, we studied the consequences of hypothyroidism on leptin production as well as leptin sensing in congenital hypothyroid TRH receptor 1 knockout (Trhr1 ko) mice and euthyroid control animals. Hypothyroid mice exhibited decreased circulating leptin levels due to a decrease in fat mass and reduced leptin expression in white adipose tissue. In neurons of the hypothalamic arcuate nucleus, hypothyroid mice showed increased leptin receptor Ob-R expression and decreased suppressor of cytokine signaling 3 transcript levels. In order to monitor putative changes in central leptin sensing, we generated hypothyroid and leptin-deficient animals by crossing hypothyroid Trhr1 ko mice with the leptin-deficient ob/ob mice. Hypothyroid Trhr1/ob double knockout mice showed a blunted response to leptin treatment with respect to body weight and food intake and exhibited a decreased activation of phospho-signal transducer and activator of transcription 3 as well as a up-regulation of suppressor of cytokine signaling 3 upon leptin treatment, particularly in the arcuate nucleus. These data indicate alterations in the intracellular processing of the leptin signal under hypothyroid conditions and thereby unravel a novel mode of action by which TH affects energy metabolism. PMID:23518925

  13. A Study of Statistical Errors in MICE

    NASA Astrophysics Data System (ADS)

    Forrest, D.; Soler, F. J. P.

    2010-03-01

    The Muon Ionization Cooling Experiment (MICE) will measure ionization cooling from a beam of muons at the Rutherford Appleton Laboratory in the UK. The aim of MICE is to measure a fractional drop in emittance, due to ionization cooling, of order 10% for a range of emittances and momenta, to an accuracy of 1%. A greater understanding of the statistical (as well as systematic) errors on emittance measurement in MICE is paramount to meeting this goal. This paper describes a study aimed at exploiting the computing power of the Grid to determine the number of muons necessary to meet the scientific goals of MICE. In this study, tens of thousands of G4MICE Monte Carlo simulations were run to determine the scaling laws that govern the fractional change in emittance as a function of the number of muons (N) in the simulation. By varying random conditions, the standard deviation of these distributions was studied as a function of N. The results of the study indicate that, due to the effect of correlations, of order 105 muons are required to meet the goal of MICE for large emittance beams, without which 106 would be required.

  14. Quantification of alcohol drinking patterns in mice.

    PubMed

    Eisenhardt, Manuela; Leixner, Sarah; Spanagel, Rainer; Bilbao, Ainhoa

    2015-11-01

    The use of mice in alcohol research provides an excellent model system for a better understanding of the genetics and neurobiology of alcohol addiction. Almost 60 years ago, alcohol researchers began to test strains of mice for alcohol preference and intake. In particular, various voluntary alcohol drinking paradigms in the home cage were developed. In mouse models of voluntary oral alcohol consumption, animals have concurrent access to water and either one or several concentrated alcohol solutions in their home cages. Although these models have high face validity, many experimental conditions require a more precise monitoring of alcohol consumption in mice in order to capture the role of specific strains or genes, or any other manipulation on alcohol drinking behavior. Therefore, we have developed a fully automated, highly precise monitoring system for alcohol drinking in mice in the home cage. This system is now commercially available. We show that this drinkometer system allows for detecting differences in drinking behavior (i) in transgenic mice, (ii) following alcohol deprivation, and (iii) following stress applications that are usually not detected by classical home-cage drinking paradigms. In conclusion, our drinkometer system allows disturbance-free and high resolution monitoring of alcohol drinking behavior. In particular, micro-drinking and circadian drinking patterns can be monitored in genetically modified and inbred strains of mice after environmental and pharmacological manipulation, and therefore this system represents an improvement in measuring behavioral features that are of relevance for the development of alcohol use disorders. PMID:26515884

  15. Normal macrophage function in copper deficient mice

    SciTech Connect

    Lukasewycz, O.A.; Kolquist, K.L.; Prohaska, J.R.

    1986-03-01

    Copper deficiency (-Cu) was produced in C57 BL and C58 mice by feeding a low copper diet (modified AIN-76A) from birth. Mice given supplemental copper in the drinking water (+Cu) served as controls. Copper status was monitored by assay of ceruloplasmin (CP) activity. Macrophages (M0) were obtained from matched +Cu and -Cu male 7 week-old mice by peritoneal lavage 3 days after thioglycollate stimulation. M0 were assayed in terms of lipopolysaccharide-induced hexose monophosphate shunt activity by monitoring /sup 14/CO/sub 2/ production from (1-/sup 14/C)-glucose and by the determination of phagocytic index using fluorescein labelled latex bead ingestion. M0 from -Cu mice were equivalent to those of +Cu mice in both these parameters. However, superoxide dismutase and cytochrome oxidase activities were both significantly lower in -Cu M0, confirming a functional copper deficiency. Previous results from this laboratory have shown that -Cu mice have a decreased antibody response to sheep erythrocyte antigens and a diminished reactivity to B and T cell mitogens. These immunological insufficiencies appear to be proportional to the severity of copper depletion as determined by CP levels. Furthermore, -Cu lymphocytes exhibit depressed mixed lymphocyte reactivity consistent with alterations at the membrane surface. The present results suggest that M0/monocytes are less severely affected than lymphocytes in copper deficiency states.

  16. Palmoplantar Keratoderma in Slurp2-Deficient Mice.

    PubMed

    Allan, Christopher M; Procaccia, Shiri; Tran, Deanna; Tu, Yiping; Barnes, Richard H; Larsson, Mikael; Allan, Bernard B; Young, Lorraine C; Hong, Cynthia; Tontonoz, Peter; Fong, Loren G; Young, Stephen G; Beigneux, Anne P

    2016-02-01

    SLURP1, a member of the lymphocyte antigen 6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. SLURP2, another secreted lymphocyte antigen 6 protein, is encoded by a gene located ?20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2-3 sequences had been replaced with lacZ and neo cassettes. Slurp2(-/-) mice exhibited hyperkeratosis on the volar surface of the paws (i.e., palmoplantar keratoderma), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are similar to those of Slurp1(-/-) mice. To solidify a link between Slurp2 deficiency and palmoplantar keratoderma and to be confident that the disease phenotypes in Slurp2(-/-) mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X(-/-)) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X(-/-) mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes. PMID:26967477

  17. Cochlear function in Prestin knockout mice.

    PubMed

    Cheatham, M A; Huynh, K H; Gao, J; Zuo, J; Dallos, P

    2004-11-01

    Gross-potential recordings in mice lacking the Prestin gene indicate that compound action potential (CAP) thresholds are shifted by approximately 45 dB at 5 kHz and by approximately 60 dB at 33 kHz. However, in order to conclude that outer hair cell (OHC) electromotility is associated with the cochlear amplifier, frequency selectivity must be evaluated and the integrity of the OHC's forward transducer ascertained. The present report demonstrates no frequency selectivity in CAP tuning curves recorded in homozygotes. In addition, CAP input-output functions indicate that responses in knockout mice approach those in controls at high levels where the amplifier has little influence. Although the cochlear microphonic in knockout mice remains approximately 12 dB below that in wild-type mice even at the highest levels, this deficit is thought to reflect hair cell losses in mice lacking prestin. A change in OHC forward transduction is not implied because knockout mice display non-linear responses similar to those in controls. For example, homozygotes exhibit a bipolar summating potential (SP) with positive responses at high frequencies; negative responses at low frequencies. Measurement of intermodulation distortion also shows that the cubic difference tone, 2f(1)-f(2), is approximately 20 dB down from the primaries in both homozygotes and their controls. Because OHCs are the sole generators of the negative SP and because 2f(1)-f(2) is also thought to originate in OHC transduction, these data support the idea that forward transduction is not degraded in OHCs lacking prestin. Finally, application of AM1-43, which initially enters hair cells through their transducer channels, produces fluorescence in wild-type and knockout mice indicating transducer channel activity in both inner and outer hair cells. PMID:15319415

  18. Susceptibility of Inbred Mice to Rickettsia parkeri

    PubMed Central

    Grasperge, Britton J.; Reif, Kathryn E.; Morgan, Timothy D.; Sunyakumthorn, Piyanate; Bynog, Joseph; Paddock, Christopher D.

    2012-01-01

    Rickettsia parkeri, a member of the spotted fever group Rickettsia, is the causative agent of American boutonneuse fever in humans. Despite the increased recognition of human cases, limited information is available regarding the infection of invertebrate and vertebrate hosts for this emerging tick-borne disease. Toward the development of a viable transmission model and to further characterize the pathology associated with R. parkeri infection, inbred mouse strains (A/J, BALB/c, C3H/HeJ, and C3H/HeN) were intravenously and intradermally inoculated with 105 low-passage-number R. parkeri (Portsmouth strain), and infection, gross pathology, and histopathology were scored. Additionally, a quantitative real-time PCR (qPCR) was performed to estimate rickettsial load in heart, lung, spleen, and liver tissues of infected mice at 19 days postinoculation. Of the A/J, BALB/c, and C3H/HeN mice, none displayed universal pathology consistent with sustained infection. Compared to age-matched control mice, the intravenously inoculated C3H/HeJ mice exhibited marked facial edema and marked splenomegaly upon gross examination, while the intradermally inoculated mice developed characteristic eschar-like lesions. The C3H/HeJ mice also exhibited the greatest concentrations of rickettsial DNA from heart, lung, liver, and spleen samples when examined by qPCR. The similarity of the pathology of human disease and sustained infection suggests that the C3H/HeJ strain of mice is a promising candidate for subsequent experiments to examine the tick transmission, dissemination, and pathology of R. parkeri rickettsiosis. PMID:22392926

  19. Retinoic acid attenuates rheumatoid inflammation in mice.

    PubMed

    Kwok, Seung-Ki; Park, Mi-Kyung; Cho, Mi-La; Oh, Hye-Jwa; Park, Eun-Mi; Lee, Dong-Gun; Lee, Jennifer; Kim, Ho-Youn; Park, Sung-Hwan

    2012-07-15

    Retinoic acid is the active vitamin A derivative and is well-known to have diverse immunomodulatory actions. In this study, we investigated the impact of all-trans retinoic acid (ATRA), a biologic key metabolite of vitamin A, on the development of arthritis and the pathophysiologic mechanisms by which ATRA might have antiarthritic effects in animal model of rheumatoid arthritis (RA; collagen-induced arthritis [CIA] in DBA/1J mice). We showed that treatment with ATRA markedly suppressed the clinical and histologic signs of arthritis in the CIA mice. It reduced the expression of IL-17 in the arthritic joints. Interestingly, Foxp3(+) regulatory T cells were markedly increased and IL-17-producing CD4(+) T cells (Th17 cells) were decreased in the spleens of ATRA-treated mice. In vitro treatment with ATRA induced the expression of Foxp3 and repressed the IL-17 expression in the CD4(+) T cells in mice. ATRA suppressed the production of total IgG and IgG2a in splenocytes that were stimulated by LPS. It also reduced serum levels of total IgG and IgG2 anti-collagen Abs and germinal center formation in CIA mice. In addition, the ATRA-treated mice showed decreased osteoclast formation in arthritic joints. Moreover, ATRA downregulated the expression of receptor activator of NF-κB ligand, the leading player of osteoclastogenesis, in the CD4(+) T cells and fibroblast-like synoviocytes from patients with RA. Furthermore, ATRA prevented both human monocytes and mice bone marrow-derived monocytes/macrophage cells from differentiating into osteoclasts. These data suggest ATRA might be an effective treatment modality for RA patients. PMID:22696440

  20. Effects of Myostatin Deletion in Aging Mice

    PubMed Central

    Morissette, Michael R.; Stricker, Janelle C.; Rosenberg, Michael A.; Buranasombati, Cattleya; Levitan, Emily B.; Mittleman, Murray A.; Rosenzweig, Anthony

    2009-01-01

    Inhibitors of myostatin, a negative regulator of skeletal muscle mass, are being developed to mitigate aging-related muscle loss. Knockout mouse studies suggest myostatin also affects adiposity, glucose handling, and cardiac growth. However, the cardiac consequences of inhibiting myostatin remain unclear. Myostatin inhibition can potentiate cardiac growth in specific settings (Morissette et al. 2006), a concern since cardiac hypertrophy is associated with adverse clinical outcomes. Therefore we examined the systemic and cardiac effects of myostatin deletion in aged mice (27-30 months old). Heart mass increased comparably in both wildtype (WT) and knockout (KO) mice. Aged KO mice maintained twice as much quadriceps mass as aged WT, however both groups lost the same percentage (36%) of adult muscle mass. Dual-energy x-ray absorptiometry (DEXA) revealed increased bone density, mineral content, and area in aged KO versus aged WT mice. Serum insulin and glucose levels were lower in KO mice. Echocardiography showed preserved cardiac function with better fractional shortening (58.1 vs 49.4%, p=0.002) and smaller LV diastolic diameters (3.41 vs 2.71, p=0.012) in KO versus WT mice. Phospholamban phosphorylation was increased 3.3-fold in KO hearts (p<0.05), without changes in total phospholamban, SERCA2a, or calsequestrin. Aged KO hearts showed less fibrosis by Masson's Trichrome staining. Thus myostatin deletion does not affect aging-related increases in cardiac mass and appears beneficial for bone density, insulin sensitivity, and heart function in senescent mice. These results suggest that clinical interventions designed to inhibit skeletal muscle mass loss with aging could have beneficial effects on other organ systems as well. PMID:19663901

  1. Dysfunctional dopaminergic neurotransmission in asocial BTBR mice

    PubMed Central

    Squillace, M; Dodero, L; Federici, M; Migliarini, S; Errico, F; Napolitano, F; Krashia, P; Di Maio, A; Galbusera, A; Bifone, A; Scattoni, M L; Pasqualetti, M; Mercuri, N B; Usiello, A; Gozzi, A

    2014-01-01

    Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits and stereotyped behaviours. Recent psychosocial and neuroimaging studies have highlighted reward-processing deficits and reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological and molecular determinants of these deficits remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about the origin and neurophysiological underpinnings of clinically relevant traits. Here we used functional magnetic resonance imaging (fMRI), behavioural and molecular readouts to probe dopamine neurotransmission responsivity in BTBR T+ Itpr3tf/J mice (BTBR), an inbred mouse line widely used to model ASD-like symptoms owing to its robust social and communication deficits, and high level of repetitive stereotyped behaviours. C57BL/6J (B6) mice were used as normosocial reference comparators. DA reuptake inhibition with GBR 12909 produced significant striatal DA release in both strains, but failed to elicit fMRI activation in widespread forebrain areas of BTBR mice, including mesolimbic reward and striatal terminals. In addition, BTBR mice exhibited no appreciable motor responses to GBR 12909. DA D1 receptor-dependent behavioural and signalling responses were found to be unaltered in BTBR mice, whereas dramatic reductions in pre- and postsynaptic DA D2 and adenosine A2A receptor function was observed in these animals. Overall these results document profoundly compromised DA D2-mediated neurotransmission in BTBR mice, a finding that is likely to have a role in the distinctive social and behavioural deficits exhibited by these mice. Our results call for a deeper investigation of the role of dopaminergic dysfunction in mouse lines exhibiting ASD-like phenotypes, and possibly in ASD patient populations. PMID:25136890

  2. Effects of myostatin deletion in aging mice.

    PubMed

    Morissette, Michael R; Stricker, Janelle C; Rosenberg, Michael A; Buranasombati, Cattleya; Levitan, Emily B; Mittleman, Murray A; Rosenzweig, Anthony

    2009-09-01

    Inhibitors of myostatin, a negative regulator of skeletal muscle mass, are being developed to mitigate aging-related muscle loss. Knock-out (KO) mouse studies suggest myostatin also affects adiposity, glucose handling and cardiac growth. However, the cardiac consequences of inhibiting myostatin remain unclear. Myostatin inhibition can potentiate cardiac growth in specific settings (Morissette et al., 2006), a concern because of cardiac hypertrophy is associated with adverse clinical outcomes. Therefore, we examined the systemic and cardiac effects of myostatin deletion in aged mice (27-30 months old). Heart mass increased comparably in both wild-type (WT) and KO mice. Aged KO mice maintained twice as much quadriceps mass as aged WT; however, both groups lost the same percentage (36%) of adult muscle mass. Dual-energy X-ray absorptiometry revealed increased bone density, mineral content, and area in aged KO vs. aged WT mice. Serum insulin and glucose levels were lower in KO mice. Echocardiography showed preserved cardiac function with better fractional shortening (58.1% vs. 49.4%, P = 0.002) and smaller left ventricular diastolic diameters (3.41 vs. 2.71, P = 0.012) in KO vs. WT mice. Phospholamban phosphorylation was increased 3.3-fold in KO hearts (P < 0.05), without changes in total phospholamban, sarco(endo)plasmic reticulum calcium ATPase 2a or calsequestrin. Aged KO hearts showed less fibrosis by Masson's Trichrome staining. Thus, myostatin deletion does not affect aging-related increases in cardiac mass and appears beneficial for bone density, insulin sensitivity and heart function in senescent mice. These results suggest that clinical interventions designed to inhibit skeletal muscle mass loss with aging could have beneficial effects on other organ systems as well. PMID:19663901

  3. Antidepressant activity of fingolimod in mice

    PubMed Central

    di Nuzzo, Luigi; Orlando, Rosamaria; Tognoli, Cristina; Di Pietro, Paola; Bertini, Giuseppe; Miele, Jessica; Bucci, Domenico; Motolese, Marta; Scaccianoce, Sergio; Caruso, Alessandra; Mauro, Gianluca; De Lucia, Carmine; Battaglia, Giuseppe; Bruno, Valeria; Fabene, Paolo Francesco; Nicoletti, Ferdinando

    2015-01-01

    Recent findings indicate that fingolimod, the first oral drug approved for the treatment of multiple sclerosis (MS), acts as a direct inhibitor of histone deacetylases (HDACs) and enhances the production of brain-derived neurotrophic factor (BDNF) in the CNS. Both mechanisms are relevant to the pathophysiology and treatment of major depression. We examined the antidepressant activity of fingolimod in mice subjected to chronic unpredictable stress (CUS), a model of reactive depression endowed with face and pharmacological validity. Chronic treatment with fingolimod (3 mg kg−1, i.p., once a day for 4 weeks) reduced the immobility time in the forced swim test (FST) in a large proportion of CUS mice. This treatment also caused anxiogenic-like effects in the social interaction test without affecting anxiety-like behavior in the elevated plus maze or spatial learning in the water maze. CUS mice showed reduced BDNF levels and enhanced HDAC2 levels in the hippocampus. These changes were reversed by fingolimod exclusively in mice that showed a behavioral response to the drug in the FST. Fingolimod treatment also enhanced H3 histone K14-acetylation and adult neurogenesis in the hippocampus of CUS mice. Fingolimod did not affect most of the parameters we have tested in unstressed control mice. The antidepressant-like activity of fingolimod was confirmed in mice chronically treated with corticosterone. These findings show for the first time that fingolimod exerts antidepressant-like effect acting in a “disease-dependent” manner, and raise the interesting possibility that the drug could relieve depressive symptoms in MS patients independently of its disease-modifying effect on MS. PMID:26171219

  4. Characteristics of scratching behavior in ADJM mice (atopic dermatitis from Japanese mice).

    PubMed

    Nakasone, Tasuku; Sato, Takumi; Matsushima, Yoshibumi; Inoue, Toshio; Kamei, Chiaki

    2015-04-01

    In order to elucidate the characteristics of scratching behavior in atopic dermatitis from Japanese mice (ADJM) mice, the effects of some antagonists of pruritogens on this behavior were studied. Both male and female ADJM mice showed frequent scratching behavior around the face, abdomen and back. The number of scratching behavior around the face was greater than on the abdomen and back, and scratching behavior in female mice was significantly more frequent than in male mice. Histamine H1 antagonist, chlorpheniramine, p.o., inhibited this behavior potently and dose-dependently. Histamine H1 antagonist with serotonin 5-TH(5-hydroxytryptamine)2 antagonist, cyproheptadine, also inhibited this behavior. However, NK1 antagonist, aprepitant, p.o., had no significant inhibitory effect even at a dose of 100 mg/kg, p.o., Mu antagonist, naloxone, and kappa agonist, nalfurafine, significantly inhibited this behavior at doses of 0.3 mg/kg, s.c., and 0.01 mg/kg, p.o., respectively. Histamine contents in the skin of ADJM mice were significantly higher than in BALB/c mice. These results strongly indicate that scratching behavior in ADJM mice is related with histamine H1, opioid mu and opioid kappa receptors. PMID:25578901

  5. Seasonal acclimation of prairie deer mice

    NASA Astrophysics Data System (ADS)

    Andrews, R. V.; Belknap, R. W.

    1993-12-01

    Prairie deer mice responded to long nights by reducing their metabolic rates, core temperatures, thermal conductances and incremental metabolic responses to cold stimulus, while increasing their capacities for nonshivering thermogenesis. Some winter animals spontaneously entered daily torpor in the mornings and thereby further reduced their metabolic rates and core temperatures. Provision of exogenous melatonin (by subdermal implants) mimiced short photoperiod effects on metabolic rates and core temperatures of wild-caught, laboratory maintained animals. Provision of supplemental dietary tryptophan to laboratory animals conditioned to natural light cycles mimiced metabolic effects of long nights in summer animals, and further reduced metabolic rates of winter mice, but did not affect their core temperature levels. Newly caught, laboratory maintained deer mice responded to natural seasonal clues of shortphotoperiod and increased dietary tryptophan by reducing their resting energy requirements through both lower metabolic and lower core temperature levels. Short photoperiod and seasonal change also promoted gonadal involution, and resulted in more socially tolerant huddling by mice with reduced core temperature. Reduced 24-hour LH excretion rates were also observed in winter animals which were exposed to seasonal light cycles at warm (25°C) room temperatures. We propose that seasonal acclimatization involves pineal effects on sex hormone-influenced social behaviors and on resting metabolism. These effects serve to conserve resting energy expenditure and promote hypothermic insulation by wild prairie deer mice.

  6. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    PubMed

    Zempo, Hirofumi; Suzuki, Jun-Ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress. PMID:26657007

  7. Ppp2ca knockout in mice spermatogenesis.

    PubMed

    Pan, Xiaoyun; Chen, Xia; Tong, Xin; Tang, Chao; Li, Jianmin

    2015-04-01

    Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase involved in meiosis, mitosis, sperm capacitation, and apoptosis. Abberant activity of PP2A has been associated with a number of diseases. The homolog PPP2CA and PPP2CB can each function as the phosphatase catalytic subunit generally referred to as PP2AC. We generated a Ppp2ca conditional knockout (CKO) in C57BL/6J mice. Exon 2 of Ppp2ca was knocked out in a spatial or temporal-specific manner in primordial germ cells at E12.5. This Ppp2ca-null mutation caused infertility in male C57BL/6J mice. These CKO mice provide a powerful tool to study the mechanisms of Ppp2ca in development and disease. PMID:25628439

  8. The superconducting solenoid magnets for MICE

    SciTech Connect

    Green, Michael A.

    2002-12-22

    The Muon Ionization Cooling Experiment (MICE) is a channel of superconducting solenoid magnets. The magnets in MICE are around the RF cavities, absorbers (liquid or solid) and the primary particle detectors [1], [2]. The MICE superconducting solenoid system consists of eighteen coils that are grouped in three types of magnet assemblies. The cooling channel consists of two complete cell of an SFOFO cooling channel. Each cell consists of a focusing coil pair around an absorber and a coupling coil around a RF cavity that re-accelerates the muons to their original momentum. At the ends of the experiment are uniform field solenoids for the particle detectors and a set of matching coils used to match the muon beam to the cooling cells. Three absorbers are used instead of two in order to shield the detectors from dark currents generated by the RF cavities at high operating acceleration gradients.

  9. Ghrelin reverses experimental diabetic neuropathy in mice

    SciTech Connect

    Kyoraku, Itaru; Shiomi, Kazutaka; Kangawa, Kenji; Nakazato, Masamitsu

    2009-11-20

    Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin {alpha}, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

  10. Payload Processing for Mice Drawer System

    NASA Technical Reports Server (NTRS)

    Brown, Judy

    2007-01-01

    Experimental payloads flown to the International Space Station provide us with valuable research conducted in a microgravity environment not attainable on earth. The Mice Drawer System is an experiment designed by Thales Alenia Space Italia to study the effects of microgravity on mice. It is designed to fly to orbit on the Space Shuttle Utilization Logistics Flight 2 in October 2008, remain onboard the International Space Station for approximately 100 days and then return to earth on a following Shuttle flight. The experiment apparatus will be housed inside a Double Payload Carrier. An engineering model of the Double Payload Carrier was sent to Kennedy Space Center for a fit check inside both Shuttles, and the rack that it will be installed in aboard the International Space Station. The Double Payload Carrier showed a good fit quality inside each vehicle, and Thales Alenia Space Italia will now construct the actual flight model and continue to prepare the Mice Drawer System experiment for launch.

  11. Magnetic biomineralisation in Huntington's disease transgenic mice

    NASA Astrophysics Data System (ADS)

    Beyhum, W.; Hautot, D.; Dobson, J.; Pankhurst, Q. A.

    2005-01-01

    The concentration levels of biogenic magnetite nanoparticles in transgenic R6/2 Huntington's disease (HD) mice have been investigated, using seven control and seven HD mice each from an 8 week-old litter and from a 12 week-old litter. Hysteresis and isothermal remnant magnetisation data were collected on a SQUID magnetometer, and analysed using a model comprising dia/paramagnetic, ferrimagnetic and superparamagnetic contributions, to extract the magnetite and ferritin concentrations present. It was found that magnetite was present in both superparamagnetic and blocked states. A larger spread and higher concentration of magnetite levels was found in the diseased mice for both the 8 week-old and 12 week-old batches, compared to the controls.

  12. Chronic fatal pneumocystosis in nude mice.

    PubMed

    Ueda, K; Goto, Y; Yamazaki, S; Fujiwara, K

    1977-12-01

    A chronic pulmonary disease was encountered in nude mice of a barrier sustained colony, and Pneumocystis carinii was identified as the causative agent histopathologically as well as on impression smear preparations in the affected lungs. Fatal infection was seen only in old nude mice aged more than 6 months, while focal pulmonary lesions were developed without clinical signs in young adult nudes 2 to 3 months of age. The lesions produced in aged nude mice were characterized by propagation of mononuclear cells with the presence of foamy masses of P. carinii. Heterozygous littermates were much less susceptible to the infection but pneumocystic lesions could be produced readily by multiple treatment with immunosuppressants. The infection could be transmitted without immunosuppressant to non-infected nudes but not to heterozygous littermates after intranasal inoculation of affected tissue emulsion or by cage mating with severely affected nudes. PMID:305493

  13. Phenylthiocarbamide produces conditioned taste aversions in mice.

    PubMed

    St John, Steven J; Pour, Lindsay; Boughter, John D

    2005-06-01

    Previous work has demonstrated that SWR/J (SW) mice avoid phenylthiocarbamide (PTC) to a greater degree than C3HeB/FeJ mice in 48 h, two-bottle preference tests given in ascending series. The authors hypothesized, based also on previous work, that SW mice might form a conditioned taste aversion over time due to the toxic properties of PTC. We directly tested this hypothesis by attempting to condition a taste aversion to sucrose by injections of PTC. In experiment 1, PTC was nearly as effective as a strong dose of LiCl in reducing sucrose drinking. In experiment 2, the sucrose aversions were parametrically modified by both sucrose concentration and PTC dose, a hallmark of conditioned taste aversion. We conclude that PTC can cause a conditioned taste aversion and discuss the importance of considering toxic effects of aversive tastants when analyzing behavioral strain differences. PMID:15800216

  14. NAD metabolism in HPRT-deficient mice

    PubMed Central

    Jacomelli, Gabriella; Di Marcello, Federica; Notarantonio, Laura; Sestini, Silvia; Cerboni, Barbara; Bertelli, Matteo; Pompucci, Giuseppe; Jinnah, Hyder A.

    2016-01-01

    The activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) is virtually absent in Lesch-Nyhan disease (LND), an X-linked genetic disorder characterized by uric acid accumulation and neurodevelopmental dysfunction. The biochemical basis for the neurological and behavioral abnormalities have not yet been completely explained. Prior studies of cells from affected patients have shown abnormalities of NAD metabolism. In the current studies, NAD metabolism was evaluated in HPRT gene knock-out mice. NAD content and the activities of the enzymes required for synthesis and breakdown of this coenzyme were investigated in blood, brain and liver of HPRT− and control mice. NAD concentration and enzyme activities were found to be significantly increased in liver, but not in brain or blood of the HPRT− mice. These results demonstrate that changes in NAD metabolism occur in response to HPRT deficiency depending on both species and tissue type. PMID:19319672

  15. Mice infer probabilistic models for timing

    PubMed Central

    Li, Yi; Dudman, Joshua Tate

    2013-01-01

    Animals learn both whether and when a reward will occur. Neural models of timing posit that animals learn the mean time until reward perturbed by a fixed relative uncertainty. Nonetheless, animals can learn to perform actions for reward even in highly variable natural environments. Optimal inference in the presence of variable information requires probabilistic models, yet it is unclear whether animals can infer such models for reward timing. Here, we develop a behavioral paradigm in which optimal performance required knowledge of the distribution from which reward delays were chosen. We found that mice were able to accurately adjust their behavior to the SD of the reward delay distribution. Importantly, mice were able to flexibly adjust the amount of prior information used for inference according to the moment-by-moment demands of the task. The ability to infer probabilistic models for timing may allow mice to adapt to complex and dynamic natural environments. PMID:24082097

  16. Multiple Scattering Measurements in the MICE Experiment

    SciTech Connect

    Carlisle, T.; Cobb, J.; Neuffer, D.; /Fermilab

    2012-05-01

    The international Muon Ionization Cooling Experiment (MICE), under construction at RAL, will test a prototype cooling channel for a future Neutrino Factory or Muon Collider. The cooling channel aims to achieve, using liquid hydrogen absorbers, a 10% reduction in transverse emittance. The change in 4D emittance will be determined with an accuracy of 1% by measuring muons individually. Step IV of MICE will make the first precise emittance-reduction measurements of the experiment. Simulation studies using G4MICE, based on GEANT4, find a significant difference in multiple scattering in low Z materials, compared with the standard expression quoted by the Particle Data Group. Direct measurement of multiple scattering using the scintillating-fibre trackers is found to be possible, but requires the measurement resolution to be unfolded from the data.

  17. Splenic melanosis in agouti and black mice.

    PubMed

    Michalczyk-Wetula, Dominika; Wieczorek, Justyna; Płonka, Przemysław M

    2015-01-01

    An interesting example of extradermal deposition of melanin in vertebrates, notably in mammals, is splenic melanosis. In particular, if the phenomenon of splenic melanosis is correlated with hair or skin pigmentation, it must reflect the amount and perhaps the quality of pigment produced in hair follicle melanocytes. The present paper is our first study on splenic pigmentation in mice of phenotype agouti. We used untreated mixed background mice C57BL/6;129/SvJ (black - a/a, agouti - A/a, A/A), and as a control - black C57BL/6 and agouti fur from 129/SvJ mice, Mongolian gerbils (Meriones unguiculatus) and golden hamsters (Mesocricetus auratus). After euthanasia skin and spleen was evaluated macroscopically, photographed and collected for further analysis using Fontana-Masson and hematoxylin-eosin staining and electron paramagnetic resonance (EPR) at X-band. Spleens of the agouti mice revealed splenic melanosis but were slightly weaker pigmented than their black counterparts, while the presence of pheomelanin was difficult to determine. The fur of both phenotypes was of similar melanin content, with the same tendency as in the spleens. The contribution of pheomelanin in the agouti fur was on the border of detectability by EPR. Histological and EPR analysis confirmed the presence of melanin in the melanotic spleens. The shape of the EPR signal showed a dominance of eumelanin in fur and in melanized spleens in both phenotypes of mice. Therefore, splenic melanosis does reflect the hair follicle pigmentation not only in black, but also in agouti mice. PMID:26291042

  18. Xanthohumol improved cognitive flexibility in young mice

    PubMed Central

    Zamzow, Daniel R; Elias, Valerie; Legette, LeeCole L; Choi, Jaewoo; Stevens, J. Fred; Magnusson, Kathy R

    2014-01-01

    The protein palmitoylation cycle has been shown to be important for protein signaling and synaptic plasticity. Data from our lab showed a change in the palmitoylation status of certain proteins with age. A greater percentage of the NMDA receptor subunits GluN2A and GluN2B, along with Fyn and PSD95 proteins, were palmitoylated in the old mice. The higher level of protein palmitoylation was also associated with poorer learning scores. Xanthohumol is a prenylated flavonoid that has been shown to increase beta-oxidation in the livers of rodents, decreasing circulating free fatty acids in the serum. What is not known is whether the application of xanthohumol could influence the palmitoylation status of proteins. In this study, young and old mice were fed a diet supplemented with xanthohumol for 8 weeks. Spatial memory was assessed with the Morris water maze and protein palmitoylation quantified. The young xanthohumol-treated mice showed a significant improvement in cognitive flexibility. However, this appeared to be associated with the young control mice, on a defined, phytoestrogen-deficient diet, performing as poorly as the old mice and xanthohumol reversing this effect. The old mice receiving xanthohumol did not significantly improve their learning scores. Xanthohumol treatment was unable to affect the palmitoylation of NMDA receptor subunits and associated proteins assessed in this study. This evidence suggests that xanthohumol may play a role in improving cognitive flexability in young animals, but it appears to be ineffective in adjusting the palmitoylation status of neuronal proteins in aged individuals. PMID:25192637

  19. Intermittent hypoxia induces hyperlipidemia in lean mice.

    PubMed

    Li, Jianguo; Thorne, Laura N; Punjabi, Naresh M; Sun, Cheuk-Kwan; Schwartz, Alan R; Smith, Philip L; Marino, Rafael L; Rodriguez, Annabelle; Hubbard, Walter C; O'Donnell, Christopher P; Polotsky, Vsevolod Y

    2005-09-30

    Obstructive sleep apnea, a syndrome leading to recurrent intermittent hypoxia (IH), has been associated previously with hypercholesterolemia, independent of underlying obesity. We examined the effects of experimentally induced IH on serum lipid levels and pathways of lipid metabolism in the absence and presence of obesity. Lean C57BL/6J mice and leptin-deficient obese C57BL/6J-Lep(ob) mice were exposed to IH for five days to determine changes in serum lipid profile, liver lipid content, and expression of key hepatic genes of lipid metabolism. In lean mice, exposure to IH increased fasting serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, phospholipids (PLs), and triglycerides (TGs), as well as liver TG content. These changes were not observed in obese mice, which had hyperlipidemia and fatty liver at baseline. In lean mice, IH increased sterol regulatory element binding protein 1 (SREBP-1) levels in the liver, increased mRNA and protein levels of stearoyl-coenzyme A desaturase 1 (SCD-1), an important gene of TG and PL biosynthesis controlled by SREBP-1, and increased monounsaturated fatty acid content in serum, which indicated augmented SCD-1 activity. In addition, in lean mice, IH decreased protein levels of scavenger receptor B1, regulating uptake of cholesterol esters and HDL by the liver. We conclude that exposure to IH for five days increases serum cholesterol and PL levels, upregulates pathways of TG and PL biosynthesis, and inhibits pathways of cholesterol uptake in the liver in the lean state but does not exacerbate the pre-existing hyperlipidemia and metabolic disturbances in leptin-deficient obesity. PMID:16123334

  20. Ocular Phenotype of Fbn2-Null Mice

    PubMed Central

    Shi, Yanrong; Tu, Yidong; Mecham, Robert P.; Bassnett, Steven

    2013-01-01

    Purpose. Fibrillin-2 (Fbn2) is the dominant fibrillin isoform expressed during development of the mouse eye. To test its role in morphogenesis, we examined the ocular phenotype of Fbn2−/− mice. Methods. Ocular morphology was assessed by confocal microscopy using antibodies against microfibril components. Results. Fbn2−/− mice had a high incidence of anterior segment dysgenesis. The iris was the most commonly affected tissue. Complete iridal coloboma was present in 37% of eyes. Dyscoria, corectopia and pseudopolycoria were also common (43% combined incidence). In wild-type (WT) mice, fibrillin-2-rich microfibrils are prominent in the pupillary membrane (PM) during development. In Fbn2-null mice, the absence of Fbn2 was partially compensated for by increased expression of fibrillin-1, although the resulting PM microfibrils were disorganized, compared with WTs. In colobomatous adult Fbn2−/− eyes, the PM failed to regress normally, especially beneath the notched region of the iris. Segments of the ciliary body were hypoplastic, and zonular fibers, although relatively plentiful, were unevenly distributed around the lens equator. In regions where the zonular fibers were particularly disturbed, the synchronous differentiation of the underlying lens fiber cells was affected. Conclusions. Fbn2 has an indispensable role in ocular morphogenesis in mice. The high incidence of iris coloboma in Fbn2-null animals implies a previously unsuspected role in optic fissure closure. The observation that fiber cell differentiation was disturbed in Fbn2−/− mice raises the possibility that the attachment of zonular fibers to the lens surface may help specify the equatorial margin of the lens epithelium. PMID:24130178

  1. The Memory of MICE: The Configuration Database

    NASA Astrophysics Data System (ADS)

    Wilson, A. J.; Colling, D. J.; Hanlet, P.

    2012-12-01

    The configuration database (CDB) is the memory of the Muon Ionisation Cooling Experiment (MICE). Its principle aim is to store temporal data associated with the running of the experiment; these data are used throughout the life cycle of experiment, from running the experiment through data analysis. The CDB also serves as a moderator in the MICE state machine by defining allowable operating states of subsystems depending on the overall state of MICE and other subsystems. Master and slave CDBs, with multiple mirrored pair raid arrays, have been set up in different parts of the site to increase resilience, as well as off site backups. Access to the CDB is via a Python API, which communicates with a WSDL interface provided by a web-service on the CDB. The priority is to ensure availability of the CDB in the experiment control room. The master CDB is located in the MICE control where it is only used by the running experiment. In the event of the failure of the master, the slave can easily be promoted to master. Read only access to the CDB for data analysis and reconstruction is provided by the slave which has an up to the minute copy of the data. As MICE is a precision experiment which will measure a 10% muon cooling effect with 1% precision, it is imperative that we minimize our systematic errors; the CDB will ensure reproducible and documented running conditions in a highly resilient manner. A description of the hardware and software used in the the MICE CDB will be described in what follows.

  2. Mapping Pathological Phenotypes in Reelin Mutant Mice

    PubMed Central

    Michetti, Caterina; Romano, Emilia; Altabella, Luisa; Caruso, Angela; Castelluccio, Paolo; Bedse, Gaurav; Gaetani, Silvana; Canese, Rossella; Laviola, Giovanni; Scattoni, Maria Luisa

    2014-01-01

    Autism Spectrum Disorders (ASD) are neurodevelopmental disorders with multifactorial origin characterized by social communication deficits and the presence of repetitive behaviors/interests. Several studies showed an association between the reelin gene mutation and increased risk of ASD and a reduced reelin expression in some brain regions of ASD subjects, suggesting a role for reelin deficiency in ASD etiology. Reelin is a large extracellular matrix glycoprotein playing important roles during development of the central nervous system. To deeply investigate the role of reelin dysfunction as vulnerability factor in ASD, we assessed the behavioral, neurochemical, and brain morphological features of reeler male mice. We recently reported a genotype-dependent deviation in the ultrasonic vocal repertoire and a general delay in motor development of reeler pups. We now report that adult male heterozygous (Het) reeler mice did not show social behavior and communication deficits during male–female social interactions. Wildtype and Het mice showed a typical light/dark locomotor activity profile, with a peak during the central interval of the dark phase. However, when faced with a mild stressful stimulus (a saline injection) only Het mice showed an over response to stress. In addition to the behavioral studies, we conducted high performance liquid chromatography and magnetic resonance imaging and spectroscopy to investigate whether reelin mutation influences brain monoamine and metabolites levels in regions involved in ASD. Low levels of dopamine in cortex and high levels of glutamate and taurine in hippocampus were detected in Het mice, in line with clinical data collected on ASD children. Altogether, our data detected subtle but relevant neurochemical abnormalities in reeler mice supporting this mutant line, particularly male subjects, as a valid experimental model to estimate the contribution played by reelin deficiency in the global ASD neurobehavioral phenotype. PMID:25237666

  3. Erythrocyte survival in normal mice and in mice with autoimmune haemolytic anaemia

    PubMed Central

    Lindsey, E. S.; Donaldson, G. W. K.; Woodruff, M. F. A.

    1966-01-01

    Erythrocyte survival has been studied in a strain of mice which develop autoimmune haemolytic anaemia in adult life (NZB/B1), and also in CBA and C57B1 mice, using one or both of two radioactive isotope labels, 51Cr and 32P. Erythrocyte survival is customarily expressed as the half-life but this is unsatisfactory for purposes of statistical comparison and we have used instead a parameter `κ' which represents the slope of the line obtained when: log(Counts per unit haemoglobin on day t)/(Counts per unit haemoglobin on day 0) is plotted against time. Young NZB/B1 mice yield values of κ intermediate between those obtained in CBA and C57B1 mice, and may reasonably be judged to show normal erythrocyte survival. On the other hand, in older NZB/B1 mice which are strongly Coombs positive and show reticulocytosis and anaemia, erythrocyte survival is greatly shortened. The survival of erythrocytes transfused to NZB/B1 recipients from isogeneic donors was found to be similar to that of the recipient's own erythrocytes, irrespective of whether or not the donor was Coombs positive or showed other evidence of haemolytic activity. The values of κ obtained in NZB/B1 mice were essentially the same with both labels; in CBA mice, however, a significant difference was observed. PMID:5915102

  4. Molecular basis of cleft palates in mice

    PubMed Central

    Funato, Noriko; Nakamura, Masataka; Yanagisawa, Hiromi

    2015-01-01

    Cleft palate, including complete or incomplete cleft palates, soft palate clefts, and submucosal cleft palates, is the most frequent congenital craniofacial anomaly in humans. Multifactorial conditions, including genetic and environmental factors, induce the formation of cleft palates. The process of palatogenesis is temporospatially regulated by transcription factors, growth factors, extracellular matrix proteins, and membranous molecules; a single ablation of these molecules can result in a cleft palate in vivo. Studies on knockout mice were reviewed in order to identify genetic errors that lead to cleft palates. In this review, we systematically describe these mutant mice and discuss the molecular mechanisms of palatogenesis. PMID:26322171

  5. Neospora caninum: identification of 19-, 38-, and 40-kDa surface antigens and a 33-kDa dense granule antigen using monoclonal antibodies.

    PubMed

    Schares, G; Dubremetz, J F; Dubey, J P; Bärwald, A; Loyens, A; Conraths, F J

    1999-06-01

    Neospora caninum, a coccidian parasite closely related to Toxoplasma gondii, can infect a broad host range and is regarded as an important cause of bovine abortion worldwide. In the present study, four antigens of N. caninum were partially characterized using monoclonal antibodies. Immunofluorescence of viable tachyzoites as well as the immunoprecipitation of antigens extracted from tachyzoites previously labeled by surface biotinylation revealed that three of these antigens with apparent molecular weights of 40, 38, and 19 kDa are located in the outer surface membrane of this parasite stage. Further evidence for the surface localization of the 38-kDa antigen was obtained by immunoelectron microscopy. In addition to the surface molecules, an antigen located in dense granules and in the tubular network of the parasitophorous vacuole was detected by another monoclonal antibody. When tachyzoite antigens separated under nonreducing conditions were probed on Western blots, this antibody reacted mainly with a 33-kDa antigen. Immunohistochemical analysis of infected tissue sections indicated that the 33-kDa dense granule antigen is present in both tachyzoites and bradyzoites, while the 38-kDa surface antigen from tachyzoites seems to be absent in bradyzoites. PMID:10366536

  6. Microdialysis in freely moving mice: determination of acetylcholine, serotonin and noradrenaline release in galanin transgenic mice.

    PubMed

    Kehr, J; Yoshitake, T; Wang, F H; Wynick, D; Holmberg, K; Lendahl, U; Bartfai, T; Yamaguchi, M; Hökfelt, T; Ogren, S O

    2001-08-15

    In the present study, we describe micro-surgical methods for simultaneous implantation of a microdialysis probe and an intraventricular injection cannula via their respective guide cannulas into the mouse brain. Basal and stimulated release of acetylcholine (ACh), serotonin (5-HT) and noradrenaline (NA) was determined in the ventral hippocampus of freely moving mice. NA and 5-HT were determined in one run by a newly developed HPLC method based on precolumn derivatization with benzylamine and fluorescence detection. The mice with a loss-of-function mutation of the galanin gene (KO) and the mice that over-expressed galanin (OE) were studied. No significant differences in basal, potassium-stimulated or scopolamine-induced extracellular ACh levels were observed in 4-month-old wild-type (WT) and KO mice. In the aged, 10-month-old animals, the basal extracellular ACh levels were significantly reduced in both WT and KO groups. Galanin (1 nmol i.c.v.) caused a significant reduction of basal extracellular NA by about 40% in both WT and galanin OE mice, however, in the latter group the effect was delayed by almost 2 h. A 10-min forced swimming stress caused a higher increase in release of NA and 5-HT in the OE group than in the corresponding WT mice. Finally, venlafaxin (10 mg/kg i.p.) increased extracellular NA to 400% of the control values in the CBA mice, but only to 250% in the C57BL mice. It is concluded that galanin may play an important role in the cholinergic mechanisms underlying cognitive disorders. Furthermore, modulation by galanin and by behavioral activation, of NA and 5-HT neurotransmission in galanin over-expressing mice indicates its possible role in the aetiology of mood disorders. PMID:11489302

  7. Increased Adiposity in Annexin A1-Deficient Mice

    PubMed Central

    Akasheh, Rand T.; Pini, Maria; Pang, Jingbo; Fantuzzi, Giamila

    2013-01-01

    Production of Annexin A1 (ANXA1), a protein that mediates the anti-inflammatory action of glucocorticoids, is altered in obesity, but its role in modulation of adiposity has not yet been investigated. The objective of this study was to investigate modulation of ANXA1 in adipose tissue in murine models of obesity and to study the involvement of ANXA1 in diet-induced obesity in mice. Significant induction of ANXA1 mRNA was observed in adipose tissue of both C57BL6 and Balb/c mice with high fat diet (HFD)-induced obesity versus mice on chow diet. Upregulation of ANXA1 mRNA was independent of leptin or IL-6, as demonstrated by use of leptin-deficient ob/ob mice and IL-6 KO mice. Compared to WT mice, female Balb/c ANXA1 KO mice on HFD had increased adiposity, as indicated by significantly elevated body weight, fat mass, leptin levels, and adipocyte size. Whereas Balb/c WT mice upregulated expression of enzymes involved in the lipolytic pathway in response to HFD, this response was absent in ANXA1 KO mice. A significant increase in fasting glucose and insulin levels as well as development of insulin resistance was observed in ANXA1 KO mice on HFD compared to WT mice. Elevated plasma corticosterone levels and blunted downregulation of 11-beta hydroxysteroid dehydrogenase type 1 in adipose tissue was observed in ANXA1 KO mice compared to diet-matched WT mice. However, no differences between WT and KO mice on either chow or HFD were observed in expression of markers of adipose tissue inflammation. These data indicate that ANXA1 is an important modulator of adiposity in mice, with female ANXA1 KO mice on Balb/c background being more susceptible to weight gain and diet-induced insulin resistance compared to WT mice, without significant changes in inflammation. PMID:24312665

  8. Increased adiposity in annexin A1-deficient mice.

    PubMed

    Akasheh, Rand T; Pini, Maria; Pang, Jingbo; Fantuzzi, Giamila

    2013-01-01

    Production of Annexin A1 (ANXA1), a protein that mediates the anti-inflammatory action of glucocorticoids, is altered in obesity, but its role in modulation of adiposity has not yet been investigated. The objective of this study was to investigate modulation of ANXA1 in adipose tissue in murine models of obesity and to study the involvement of ANXA1 in diet-induced obesity in mice. Significant induction of ANXA1 mRNA was observed in adipose tissue of both C57BL6 and Balb/c mice with high fat diet (HFD)-induced obesity versus mice on chow diet. Upregulation of ANXA1 mRNA was independent of leptin or IL-6, as demonstrated by use of leptin-deficient ob/ob mice and IL-6 KO mice. Compared to WT mice, female Balb/c ANXA1 KO mice on HFD had increased adiposity, as indicated by significantly elevated body weight, fat mass, leptin levels, and adipocyte size. Whereas Balb/c WT mice upregulated expression of enzymes involved in the lipolytic pathway in response to HFD, this response was absent in ANXA1 KO mice. A significant increase in fasting glucose and insulin levels as well as development of insulin resistance was observed in ANXA1 KO mice on HFD compared to WT mice. Elevated plasma corticosterone levels and blunted downregulation of 11-beta hydroxysteroid dehydrogenase type 1 in adipose tissue was observed in ANXA1 KO mice compared to diet-matched WT mice. However, no differences between WT and KO mice on either chow or HFD were observed in expression of markers of adipose tissue inflammation. These data indicate that ANXA1 is an important modulator of adiposity in mice, with female ANXA1 KO mice on Balb/c background being more susceptible to weight gain and diet-induced insulin resistance compared to WT mice, without significant changes in inflammation. PMID:24312665

  9. Social and Sexual Behaivours of Mice in Partial Gravity

    NASA Astrophysics Data System (ADS)

    Aou, Shuji; Hasegawa, Katsuya; Kumei, Yasuhiro; Inoue, Katarzyna; Zeredo, Jorge; Narikiyo, Kimiya; Watanabe, Yuuki

    2012-07-01

    We examined social and sexual behaviours in normal ICR mice, C57BL mice and obese db/db mice lacking leptin receptors in low gravity conditions using parabolic-flight to generate graded levels of partial gravity. Although both normal and obese mice floated with vigorous limb and tail movements when a floor is smooth in microgravity but they were rather stable if a floor is cover by carpet. Obese mice were more stable and socially contacted longer with a partner in low-gravity conditions. When they returned to the home cage after parabolic flights, obese mice started to eat sooner without restless behaviour, while control mice showed restless behaviour without eating. Face grooming, an indicator of stress response, was found more often in the control mice than the obese mice. Obese mice returned to resting condition faster than the control. We also analysed sexual behaviour of ICR mice and C57BL mice but not db/db mice since they are sexually inactive. Social and sexual behaviour could be evaluated in partial gravity conditions to get basic data concerning whether rodents can communicate and reproduce in Moon, Mars and space or not. Supported by Grant-in-Aid for Exploratory Research (JSPS) to S Aou and FY2010 grants from JAXA and Japan Society for Promotion of Science to Y. Kumei.

  10. Biochemical and microscopic analysis of sperm in copper deficient mice

    SciTech Connect

    Everett, J.; Jackson, P.; Allison, S.

    1986-03-01

    The Mottle Brindle Mouse Syndrome is a disease in mice which mimics Menkes Syndrome in humans. Treatment of affected male mice has led to varying survival rates in mice and few attempts have led to the development of virile male offsprings in mice and none in humans. In this study the authors examined sperm produced by Brindle mice in an attempt to ascertain reasons for the observed failure of the Brindle mice to reproduce. Microscopic analysis revealed that sperm counts in these mice are higher than sperm counts of the C57/BL or the C57/6J (normal) mice. Microscopically, sperm from Brindle mice showed changes in the acrosomal and flagellum regions. Motility of these sperm were 10% to 50% that of sperm from normal mice. Biochemically, cytochrome oxidase activity was 10% to 50% of the activity seen in normal mice. Hexokinase activity and pyruvate dehydrogenase activity was equal to that observed in normal mice. These observations suggest that infertility in Brindle male mice is due to an impairment of testicular copper transport which leads to a decline in copper dependent processes.

  11. Tolerance to ethanol hypothermia in HOT and COLD mice.

    PubMed

    Crabbe, J C

    1994-02-01

    COLD and HOT mice have been selected to be sensitive or resistant, respectively, to the acute hypothermic effect of ethanol. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. By administering several doses of ethanol and recording multiple postdrug temperatures, in the current study we equated the selected lines for area under the curve describing initial hypothermic response over time, a measure reflecting both maximal hypothermia achieved and the duration of total hypothermic response. The dose-response function for COLD mice was much steeper than that for HOT mice, and HOT mice recovered to baseline body temperatures more slowly. Doses were administered daily for 5 days. Both lines developed tolerance to ethanol hypothermia. The magnitude of tolerance developed was greater in COLD than in HOT mice. At higher doses, HOT mice showed a progressively enhanced hypothermic response over days (i.e., sensitization). PMID:8198225

  12. The gut microbiota regulates bone mass in mice.

    PubMed

    Sjögren, Klara; Engdahl, Cecilia; Henning, Petra; Lerner, Ulf H; Tremaroli, Valentina; Lagerquist, Marie K; Bäckhed, Fredrik; Ohlsson, Claes

    2012-06-01

    The gut microbiota modulates host metabolism and development of immune status. Here we show that the gut microbiota is also a major regulator of bone mass in mice. Germ-free (GF) mice exhibit increased bone mass associated with reduced number of osteoclasts per bone surface compared with conventionally raised (CONV-R) mice. Colonization of GF mice with a normal gut microbiota normalizes bone mass. Furthermore, GF mice have decreased frequency of CD4(+) T cells and CD11b(+) /GR 1 osteoclast precursor cells in bone marrow, which could be normalized by colonization. GF mice exhibited reduced expression of inflammatory cytokines in bone and bone marrow compared with CONV-R mice. In summary, the gut microbiota regulates bone mass in mice, and we provide evidence for a mechanism involving altered immune status in bone and thereby affected osteoclast-mediated bone resorption. Further studies are required to evaluate the gut microbiota as a novel therapeutic target for osteoporosis. PMID:22407806

  13. Chronic antigen-antibody-complex glomerulonephritis in mice.

    PubMed Central

    Steward, M. W.; Collins, M. J.; Stanley, C.; Devey, M. E.

    1981-01-01

    Daily injection of human serum albumin into mice genetically selected to produce low-affinity antibody to protein antigens resulted in a more severe antigen-antibody-complex-induced glomerulonephritis than in mice producing high-affinity antibody. The low-affinity mice had higher levels of circulating antigen-antibody complexes, greater impairment of renal function and reduced reticuloendothelial clearance of 125I-PVP compared to high-affinity mice. Electron microscopy of glomeruli revealed the presence of subepithelial electron-dense deposits in low-affinity mice and predominantly subendothelial-mesangial deposits in high-affinity mice which corresponded to the predominantly capillary staining in low-affinity mice and mesangial staining in high-affinity mice by immunofluorescence. Auto-radiography of electron-microscopy sections demonstrated the presence of antigen in the electron-dense deposits, indicating that these deposits indeed contained antigen-antigen complexes. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:6459798

  14. Scientists Reduce Alzheimer's-Linked Brain Plaques in Mice

    MedlinePlus

    ... html Scientists Reduce Alzheimer's-Linked Brain Plaques in Mice Team used gene therapy, but there's no guarantee ... March 31, 2016 (HealthDay News) -- Scientists working with mice report preliminary progress in efforts to eliminate brain- ...

  15. Scientists Grow and Transplant Functioning Skin Onto Mice

    MedlinePlus

    ... html Scientists Grow and Transplant Functioning Skin Onto Mice It's a promising start, but human version may ... tissue as small as one square millimeter into mice. The scientists included a fluorescent marker in the ...

  16. Removing a Protein Prevents Obesity, Extends Lifespan in Mice

    MedlinePlus

    ... of Events Follow Us Removing a protein prevents obesity, extends lifespan in mice 9/15/2014 Page ... a protein named Foxa3 protects mice from developing obesity and type 2 diabetes as they age. Because ...

  17. Generation of Gene Knockout Mice by ES Cell Microinjection

    PubMed Central

    Longenecker, Glenn; Kulkarni, Ashok B

    2009-01-01

    This unit lists and describes protocols used in the production of chimeric mice leading to the generation of gene knockout mice. These protocols include the collection of blastocyst embryos, ES cell injection, and uterine transfer of injected blastocysts. Support protocols in the superovulation of blastocyst donor mice, generation of pseudopregnant recipients, fabrication of glass pipettes, and generation of germline mice are also included. Practical tips and solutions are mentioned to help troubleshoot problems that may occur. PMID:19731226

  18. A miniature mechanical ventilator for newborn mice.

    PubMed

    Kolandaivelu, K; Poon, C S

    1998-02-01

    Transgenic/knockout mice with pre-defined mutations have become increasingly popular in biomedical research as models of human diseases. In some instances, the resulting mutation may cause cardiorespiratory distress in the neonatal or adult animals and may necessitate resuscitation. Here we describe the design and testing of a miniature and versatile ventilator that can deliver varying ventilatory support modes, including conventional mechanical ventilation and high-frequency ventilation, to animals as small as the newborn mouse. With a double-piston body chamber design, the device circumvents the problem of air leakage and obviates the need for invasive procedures such as endotracheal intubation, which are particularly important in ventilating small animals. Preliminary tests on newborn mice as early as postnatal day O demonstrated satisfactory restoration of pulmonary ventilation and the prevention of respiratory failure in mutant mice that are prone to respiratory depression. This device may prove useful in the postnatal management of transgenic/knockout mice with genetically inflicted respiratory disorders. PMID:9475887

  19. Dopamine transporter mutant mice in experimental neuropharmacology.

    PubMed

    Gainetdinov, Raul R

    2008-06-01

    An opportunity to perform targeted genetic manipulations in mice has provided another dimension for modern pharmacological research. Genetically modified mice have become important tools to investigate functions of previously unexplored proteins, define mechanism of action of new and known pharmacological drugs, and validate novel targets for treatment of human disorders. One of the best examples of such use of genetic models in experimental pharmacology represents investigations involving mice deficient in the gene encoding the dopamine transporter (DAT). The dopamine transporter tightly regulates the extracellular dynamics of dopamine by recapturing released neurotransmitter into the presynaptic terminals, and genetic deletion of this protein results in profound alterations in both the presynaptic homeostasis and the extracellular dynamics of dopamine. By using this model of severe dopaminergic dysregulation, significant progress has been made in defining the major target of psychotropic drugs, understanding the mechanisms of their action, unraveling novel signaling events relevant for dopaminergic transmission, and mapping neuronal pathways involved in dopamine-related behaviors. Furthermore, DAT mutant mice provided an opportunity to model in vivo conditions of extreme dopaminergic dysfunction that could be relevant for human disorders such as ADHD, schizophrenia, and Parkinson's disease and, thus, could serve as test systems for developing novel treatments for these and related disorders. PMID:18057916

  20. Endogenous opiates mediate radiogenic behavioral change. [Mice

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.; White, G.A.; Gibbs, G.L.

    1983-06-10

    Exposure of C57BL/6J mice to ionizing radiation caused stereotypical locomotor hyperactivity similar to that produced by morphine. Naloxone administration prevented this radiation-induced behavioral activation. These results support the hypothesis that endorphins are involved in some aspects of radiogenic behavioral change.

  1. Immunopathogenesis of environmentally induced lupus in mice.

    PubMed

    Shaheen, V M; Satoh, M; Richards, H B; Yoshida, H; Shaw, M; Jennette, J C; Reeves, W H

    1999-10-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome defined by clinical and serologic features, including arthritis, glomerulonephritis, and certain autoantibodies such as anti-nuclear ribonucleoprotein (nRNP)/Smith antigen (Sm), DNA, and ribosomal P. Although lupus is considered primarily a genetic disorder, we recently demonstrated the induction of a syndrome strikingly similar to spontaneous lupus in many nonautoimmune strains of mice exposed to the isoprenoid alkane pristane (2,6,10,14-tetramethylpentadecane), a component of mineral oil. Intraperitoneal injection of pristane leads to the formation of lipogranulomas consisting of phagocytic cells that have engulfed the oil and collections of lymphocytes. Subsequently, pristane-treated BALB/c and SJL mice develop autoantibodies characteristic of SLE, including anti-nRNP/Sm, antiribosomal P, anti-Su, antichromatin, anti-single-stranded DNA, and anti-double-stranded DNA. This is accompanied by a severe glomerulonephritis with immune complex deposition, mesangial or mesangiocapillary proliferation, and proteinuria. All inbred mice examined appear to be susceptible to this novel form of chemically induced lupus. Pristane-induced lupus is the only inducible model of autoimmunity associated with the clinical syndrome as well as with the characteristic serologic abnormalities of SLE. Defining the immunopathogenesis of pristane-induced lupus in mice may provide insight into the causes of spontaneous (idiopathic) lupus and also may lead to information concerning possible risks associated with the ingestion or inhalation of mineral oil and exposure to hydrocarbons in the environment. PMID:10502537

  2. Bone status of acetylcholinesterase-knockout mice.

    PubMed

    Kauschke, Vivien; Kneffel, Mathias; Floel, Wolfgang; Hartmann, Sonja; Kampschulte, Marian; Dürselen, Lutz; Ignatius, Anita; Schnettler, Reinhard; Heiss, Christian; Lips, Katrin Susanne

    2015-11-01

    Acetylcholinesterase (AChE) hydrolyzes acetylcholine (ACh) to acetate and choline and thereby terminates nerve impulse transmission. ACh is also expressed in bone tissue and enhances here proliferation and differentiation of osteoblasts, which makes it interesting to investigate effects of AChE deficiency on bone. To our knowledge, this is the first study that analyzed bone of heterozygous acetylcholinesterase-knockout (AChE-KO) mice. Tibia, femur, thoracic and lumbar vertebrae of 16-week-old female heterozygous AChE-KO mice and their corresponding wildtypes (WT) were analyzed using real-time RT-PCR, dual-energy X-ray absorptiometry, biomechanics, micro-computed tomography, histology and histomorphometry. Our data revealed that heterozygous AChE-KO did not cause negative effects upon bone parameters analyzed. In contrast, the number of osteoclasts per perimeter was significantly reduced in lumbar vertebrae. In addition, we found a significant decrease in trabecular perimeter of lumbar vertebrae and cortical area fraction (Ct.Ar/Tt.Ar) in the mid-diaphysis of femurs of AChE-KO mice compared to their WT. Therefore, presumably a local homozygous knockout of AChE or AChE-inhibitor administration might be beneficial for bone formation due to ACh accumulation. However, many other bone parameters analyzed did not differ statistically significantly between AChE-KO and WT mice. That might be reasoned by the compensating effect of butyrylcholinesterase (BChE). PMID:26250336

  3. Sickness behavior is delayed in hypothyroid mice.

    PubMed

    Silva, Vanessa Cardoso; Giusti-Paiva, Alexandre

    2015-03-01

    Sickness behavior is an expression of a motivational state triggered by activation of the peripheral innate immune system, whereby an organism reprioritizes its functions to fight infection. The relationship between thyroid hormone and immune cells is complex, and additional insights are needed about the involvement of the cross-talk between thyroid hormone, the central nervous system and immune function, as demonstrated by the consequences to sickness behavior. The aim of this work was to evaluate sickness behavior in hypothyroid mice. Control mice and mice treated with propylthiouracil (PTU) for 30days (0.05%; added to drinking water) received a single dose of LPS (200μg/kg; i.p.) or saline, and the behavioral response was assessed for 24h. We provide evidence that thyroid status acts a modulator for the development of depressive-like and exploratory behaviors in mice that are subjected to an immunological challenge because the PTU pretreatment delayed the LPS-induced behavioral changes observed in an open field test and in a forced swimming test. This response was observed concomitantly with a lower thermal index until 4h after the LPS administration. This result demonstrates that thyroid status modifies behavioral responses to immune challenge and suggests that thyroid hormones are essential for the manifestation of sickness behavior during endotoxemia. PMID:25524131

  4. Progress with the MICE scintillating fiber trackers

    NASA Astrophysics Data System (ADS)

    Overton, Edward

    2013-12-01

    The International Muon Ionization Cooling Experiment (MICE) is a proof of principle demonstration of ionization cooling, for application in a future neutrino factory or muon collider. MICE is under construction at the Rutherford Appleton Laboratory (UK), where a dedicated beam line has been commissioned to transport particles produced inside the ISIS accelerator facility. The beam emittance will be measured using two scintillating fiber trackers on each side of the cooling channel, which will be mounted inside a 4 T solenoid. As particles pass through the tracker, their position will be measured at 5 stations, each of which provides a position resolution of less than 0.5 mm. The fiber trackers have been validated using cosmic ray tests, which have allowed the light yield to be found. In addition, a spare tracking station was exposed to the MICE beam, which has enabled the tracker readout to be integrated with the MICE DAQ for the first time. This test required the integration gate on the D0 AFE-IIt readout boards to be synchronized with particle arrival by using diagnostic signals from the ISIS accelerator.

  5. Progress of the MICE experiment at RAL

    NASA Astrophysics Data System (ADS)

    Bonesini, M.

    2013-04-01

    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling of a muon beam. The demonstration comprises one cell of the US Neutrino Factory Study II cooling channel. Results obtained on the construction of the beamline and its instrumentation (STEP I) will be reviewed, together with progress towards final measurements of ionization cooling (STEP IV and VI).

  6. Gnathostoma spinigerum: immunodepression in experimental infected mice.

    PubMed

    Saksirisampant, Wilai; Thaisom, Sunida; Ratanavararak, Mai; Thanomsub, Benjamas Wongsatayanon

    2012-11-01

    Mice were infected with 8- or 25-infective worms of advanced third stage Gnathostoma spinigerum larvae (L3) which were obtained from natural infected eels. On day 14, 60 and 200 post infections (PI), spleen cells of infected mice were tested for lymphoproliferative responses in vitro against the mitogen and specific L3 somatic antigen in order to clarify the cellular immune status of the host upon this nematode infection. Reduced responsiveness to Con A was observed in infected mice. These depressed responses were more pronounced in chronically infected mice (day 200, PI) than in day 14 and day 60, PI. There was no significant difference of lymphoproliferative response between groups of high (25 L3) and low (8 L3)-infective dose in the chronic readily stage. Regarding to the L3 somatic Ag stimulation, the depressed response was obviously detected in high dose and chronic infection. Our results demonstrated that in this G. spinigerum-mouse system T-cell response is defective. The depression could be reversible and was associated with active infection because it was abolished by anthelmintic (ivermectin) treatment. This study shows the involvement of Th-2 response to this nematode in regulating T cell proliferation. PMID:22947220

  7. CYTOGENETIC ANALYSES OF MICE EXPOSED TO DICHLOROMETHANE

    EPA Science Inventory

    Chromosome damage was studied in female B6C3F1 mice exposed to dichloromethane (DCM) by subcutaneous or inhalation treatments. o increase in either the frequencies of sister chromatid exchanges (SCEs) or chromosome aberrations (CAs) in bone marrow cells was observed after a singl...

  8. Unexpected regeneration in middle-aged mice.

    PubMed

    Reines, Brandon; Cheng, Lily I; Matzinger, Polly

    2009-02-01

    Complete regeneration of damaged extremities, including both the epithelium and the underlying tissues, is thought to occur mainly in embryos, fetuses, and juvenile mammals, but only very rarely in adult mammals. Surprisingly, we found that common strains of mice are able to regenerate all of the tissues necessary to completely fill experimentally punched ear holes, but only if punched at middle age. Although young postweaning mice regrew the epithelium without typical pre-scar granulation tissue, they showed only minimal regeneration of connective tissues. In contrast, mice punched at 5-11 months of age showed true amphibian-like blastema formation and regrowth of cartilage, fat, and dermis, with blood vessels, sebaceous glands, hair follicles, and, in black mice, melanocytes. These data suggest that at least partial appendage regeneration may be more common in adult mammals than previously thought and call into question the common view that regenerative ability is lost with age. The data suggest that the age at which various inbred mouse strains become capable of epimorphic regeneration may be correlated with adult body weight. PMID:19226206

  9. Of Mice and Men: Interdisciplinary Unit. Revised.

    ERIC Educational Resources Information Center

    Beck Middle School, Cherry Hill, NJ.

    "Of Mice and Men" is developed as an interdisciplinary unit to be team taught by math, science, language arts, and social studies teachers and team guidance counselors. Developed as an individualized program for middle school students, a variety of supplementary materials is provided to exemplify the types of activities suggested for students.…

  10. Altered schistosome granuloma formation in nude mice.

    PubMed

    Byram, J E; von Lichtenberg, F

    1977-09-01

    Schistosome egg-induced lesions in congenitally athymic mice differed from those found in normal heterozygous controls. Heterozygote liver granulomas were chareacterized by poorly phagocytic epithelioid macrophages, and were rich in eosinophils and fibroblasts, with peripheral lymphocytes and plasma cells. Hepatic lesions in nude mice were much smaller and lacked epithelioid macrophages, with lesions about mature eggs, typically consisting of monocytes and macrophages filled with pigment, occasional neutrophils, and rarely one or more eosinophils or giant cells. While heterozygote granulomas damaged liver cells mainly by encroachment or by their vascular effects, in the nudes hepatocytes bordering the lesions showed microvesicular cytoplasmic damage and either hydropic degeneration or focal acidophilic necrosis of individual liver cells. In heterozygotes, immunofluorescent-stainable schistosome egg antigen (SEA) was concentrated in the granuloma center. In nude mice, SEA, was distributed throughout the infiltrates and in and around hepatocytes adjacent to egg lesions corresponding to the observed pattern of hepatocyte necrosis. We conclude that, in contrast to heterozygotes, nude mice lack hypersensitivity granulomas and fail to sequester toxic egg products, this resulting in zonal hepatocellular damage. Alternative explanations include the possibility of a latent hepatitis virus being activated by the schistosome infection; however, several cogent arguments are presented against that alternative. PMID:303056

  11. Induction of experimental allergic sialadenitis in mice.

    PubMed Central

    Hayashi, Y.; Sato, M.; Hirokawa, K.

    1985-01-01

    This article reports that sialadenitis developed in female CRJ:CD-1 mice thymectomized 3 days after birth and later immunized with a homogenate of the submandibular salivary gland emulsified with complete Freund's adjuvant. Significant inflammatory changes did not develop in various control groups, including animals thymectomized at Day 3 but not immunized and animals not thymectomized on the day of birth but immunized. Because a more marked decrease of Lyt 2+ cells was found in mice thymectomized on Day 3 after birth than in neonatally thymectomized mice, thymectomy at 3 days of age is more effective for the induction of sialadenitis, presumably by markedly decreasing a population of suppressor T cells. The lesions observed in mice with sialadenitis were mostly composed of small and medium-sized lymphocytes stained by anti-Thy 1.2 and Lyt 2 antibodies and in later stages by immunoglobulin-containing cells in the periphery of inflammatory lesions. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3156505

  12. Quercetin alters energy metabolism in swimming mice.

    PubMed

    Wu, Jianquan; Gao, Weina; Wei, Jingyu; Yang, Jijun; Pu, Lingling; Guo, Changjiang

    2012-10-01

    Quercetin has been demonstrated to be effective in increasing physical endurance in mice and humans. However, the mechanisms involved are not fully understood. In this study, male Kunming mice were fed a diet containing 0.1% quercetin for 14 days before swimming for 60 min. The overall serum metabolic profile was investigated by a ¹H nuclear magnetic resonance-based metabolomic approach. Serum glucose, lactate, nonesterified fatty acids (NEFA), and nonprotein nitrogen (NPN), as well as hepatic and muscular glycogen were measured biochemically. The results of metabolomic analysis showed that swimming induced a significant change in serum metabolic profile. Relative increases in the levels of lactate, alanine, low-density lipoprotein-very low-density lipoprotein, and unsaturated fatty acids, and decreases in choline, phosphocholine, and glucose were observed after swimming. With quercetin supplementation, these changes were attenuated. The results of biochemical assays were consistent with the data obtained from metabolomic analysis, in that serum NEFA was increased while lactate and NPN decreased after exposed to quercetin in swimming mice. Similar change in NEFA was also found in liver and gastrocnemius muscle tissues. Our current findings suggest that quercetin alters energy metabolism in swimming mice and increased lipolysis may contribute to the actions of quercetin on physical endurance. PMID:22765761

  13. The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice.

    PubMed

    Cancedda, Ranieri; Liu, Yi; Ruggiu, Alessandra; Tavella, Sara; Biticchi, Roberta; Santucci, Daniela; Schwartz, Silvia; Ciparelli, Paolo; Falcetti, Giancarlo; Tenconi, Chiara; Cotronei, Vittorio; Pignataro, Salvatore

    2012-01-01

    The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages. PMID:22666312

  14. Lymphocytes from chronically stressed mice confer antidepressant-like effects to naive mice.

    PubMed

    Brachman, Rebecca A; Lehmann, Michael L; Maric, Dragan; Herkenham, Miles

    2015-01-28

    We examined whether cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and CNS function in the host. Lymphocytes from mice undergoing chronic social defeat stress or from unstressed control mice were isolated and adoptively transferred into naive lymphopenic Rag2(-/-) mice. Changes in affective behavior, hippocampal cell proliferation, microglial activation states, and blood cytokine levels were examined in reconstituted stress-naive mice. The mice receiving lymphocytes from defeated donors showed less anxiety, more social behavior, and increased hippocampal cell proliferation compared with those receiving no cells or cells from unstressed donors. Mice receiving stressed immune cells had reduced pro-inflammatory cytokine levels in the blood relative to the other groups, an effect opposite to the elevated donor pro-inflammatory cytokine profile. Furthermore, mice receiving stressed immune cells had microglia skewed toward an anti-inflammatory, neuroprotective M2-like phenotype, an effect opposite the stressed donors' M1-like pro-inflammatory profile. However, stress had no effect on lymphocyte surface marker profiles in both donor and recipient mice. The data suggest that chronic stress-induced changes in the adaptive immune system, contrary to conferring anxiety and depressive behavior, protect against the deleterious effects of stress. Improvement in affective behavior is potentially mediated by reduced peripheral pro-inflammatory cytokine load, protective microglial activity, and increased hippocampal cell proliferation. The data identify the peripheral adaptive immune system as putatively involved in the mechanisms underlying stress resilience and a potential basis for developing novel rapid-acting antidepressant therapies. PMID:25632130

  15. The Mice Drawer System (MDS) Experiment and the Space Endurance Record-Breaking Mice

    PubMed Central

    Cancedda, Ranieri; Liu, Yi; Ruggiu, Alessandra; Tavella, Sara; Biticchi, Roberta; Santucci, Daniela; Schwartz, Silvia; Ciparelli, Paolo; Falcetti, Giancarlo; Tenconi, Chiara; Cotronei, Vittorio; Pignataro, Salvatore

    2012-01-01

    The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28th, 2009. MDS returned to Earth on November 27th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages. PMID:22666312

  16. Bradykinin inhibits hepatic gluconeogenesis in obese mice.

    PubMed

    Barros, Carlos Castilho; Haro, Anderson; Russo, Fernanda Jaqueline; Schadock, Ines; Almeida, Sandro Soares; Reis, Felipe Castellani; Moraes, Milton Rocha; Haidar, Andre; Hirata, Aparecida Emiko; Mori, Marcelo; Bacurau, Reury Frank Pereira; Wrtele, Martin; Bader, Michael; Pesquero, Joao Bosco; Araujo, Ronaldo Carvalho

    2012-10-01

    The kallikrein-kinin system (KKS) has been previously linked to glucose homeostasis. In isolated muscle or fat cells, acute bradykinin (BK) stimulation was shown to improve insulin action and increase glucose uptake by promoting glucose transporter 4 translocation to plasma membrane. However, the role for BK in the pathophysiology of obesity and type 2 diabetes remains largely unknown. To address this, we generated genetically obese mice (ob/ob) lacking the BK B2 receptor (obB2KO). Despite similar body weight or fat accumulation, obB2KO mice showed increased fasting glycemia (162.3 28.2 mg/dl vs 85.3 13.3 mg/dl), hyperinsulinemia (7.71 1.75 ng/ml vs 4.09 0.51 ng/ml) and impaired glucose tolerance when compared with ob/ob control mice (obWT), indicating insulin resistance and impaired glucose homeostasis. This was corroborated by increased glucose production in response to a pyruvate challenge. Increased gluconeogenesis was accompanied by increased hepatic mRNA expression of forkhead box protein O1 (FoxO1, four-fold), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (seven-fold), phosphoenolpyruvate carboxykinase (PEPCK, three-fold) and glucose-6-phosphatase (eight-fold). FoxO1 nuclear exclusion was also impaired, as the obB2KO mice showed increased levels of this transcription factor in the nucleus fraction of liver homogenates during random feeding. Intraportal injection of BK in lean mice was able to decrease the hepatic mRNA expression of FoxO1 and PEPCK. In conclusion, BK modulates glucose homeostasis by affecting hepatic glucose production in obWT. These results point to a protective role of the KKS in the pathophysiology of type 2 diabetes mellitus. PMID:22868909

  17. An alteration of the gut-liver axis drives pulmonary inflammation after intoxication and burn injury in mice.

    PubMed

    Chen, Michael M; Zahs, Anita; Brown, Mary M; Ramirez, Luis; Turner, Jerrold R; Choudhry, Mashkoor A; Kovacs, Elizabeth J

    2014-10-01

    Approximately half of all adult burn patients are intoxicated at the time of their injury and have worse clinical outcomes than those without prior alcohol exposure. This study tested the hypothesis that intoxication alters the gut-liver axis, leading to increased pulmonary inflammation mediated by burn-induced IL-6 in the liver. C57BL/6 mice were given 1.2 g/kg ethanol 30 min prior to a 15% total body surface area burn. To restore gut barrier function, the specific myosin light chain kinase inhibitor membrane-permeant inhibitor of kinase (PIK), which we have demonstrated to reduce bacterial translocation from the gut, was administered 30 min after injury. Limiting bacterial translocation with PIK attenuated hepatic damage as measured by a 47% reduction in serum alanine aminotransferase (P < 0.05), as well as a 33% reduction in hepatic IL-6 mRNA expression (P < 0.05), compared with intoxicated and burn-injured mice without PIK. This mitigation of hepatic damage was associated with a 49% decline in pulmonary neutrophil infiltration (P < 0.05) and decreased alveolar wall thickening compared with matched controls. These results were reproduced by prophylactic reduction of the bacterial load in the intestines with oral antibiotics before intoxication and burn injury. Overall, these data suggest that the gut-liver axis is deranged when intoxication precedes burn injury and that limiting bacterial translocation in this setting attenuates hepatic damage and pulmonary inflammation. PMID:25104501

  18. An alteration of the gut-liver axis drives pulmonary inflammation after intoxication and burn injury in mice

    PubMed Central

    Chen, Michael M.; Zahs, Anita; Brown, Mary M.; Ramirez, Luis; Turner, Jerrold R.; Choudhry, Mashkoor A.

    2014-01-01

    Approximately half of all adult burn patients are intoxicated at the time of their injury and have worse clinical outcomes than those without prior alcohol exposure. This study tested the hypothesis that intoxication alters the gut-liver axis, leading to increased pulmonary inflammation mediated by burn-induced IL-6 in the liver. C57BL/6 mice were given 1.2 g/kg ethanol 30 min prior to a 15% total body surface area burn. To restore gut barrier function, the specific myosin light chain kinase inhibitor membrane-permeant inhibitor of kinase (PIK), which we have demonstrated to reduce bacterial translocation from the gut, was administered 30 min after injury. Limiting bacterial translocation with PIK attenuated hepatic damage as measured by a 47% reduction in serum alanine aminotransferase (P < 0.05), as well as a 33% reduction in hepatic IL-6 mRNA expression (P < 0.05), compared with intoxicated and burn-injured mice without PIK. This mitigation of hepatic damage was associated with a 49% decline in pulmonary neutrophil infiltration (P < 0.05) and decreased alveolar wall thickening compared with matched controls. These results were reproduced by prophylactic reduction of the bacterial load in the intestines with oral antibiotics before intoxication and burn injury. Overall, these data suggest that the gut-liver axis is deranged when intoxication precedes burn injury and that limiting bacterial translocation in this setting attenuates hepatic damage and pulmonary inflammation. PMID:25104501

  19. Second-generation antisense oligonucleotides against β-catenin protect mice against diet-induced hepatic steatosis and hepatic and peripheral insulin resistance.

    PubMed

    Popov, Violeta B; Jornayvaz, Francois R; Akgul, Emin O; Kanda, Shoichi; Jurczak, Michael J; Zhang, Dongyan; Abudukadier, Abulizi; Majumdar, Sachin K; Guigni, Blas; Petersen, Kitt Falk; Manchem, Vara Prasad; Bhanot, Sanjay; Shulman, Gerald I; Samuel, Varman T

    2016-03-01

    Although mutations in the Wnt/β-catenin signaling pathway are linked with the metabolic syndrome and type 2 diabetes in humans, the mechanism is unclear. High-fat-fed male C57BL/6 mice were treated for 4 wk with a 2'-O-methoxyethyl chimeric antisense oligonucleotide (ASO) to decrease hepatic and adipose expression of β-catenin. β-Catenin mRNA decreased by ≈80% in the liver and by 70% in white adipose tissue relative to control ASO-treated mice. β-Catenin ASO improved hepatic insulin sensitivity and increased insulin-stimulated whole body glucose metabolism, as assessed during hyperinsulinemic-euglycemic clamp in awake mice. β-Catenin ASO altered hepatic lipid composition in high-fat-fed mice. There were reductions in hepatic triglyceride (44%, P < 0.05) and diacylglycerol content (60%, P < 0.01) but a 30% increase in ceramide content (P < 0.001). The altered lipid content was attributed to decreased expression of sn-1,2 diacylglycerol acyltransferase and mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase and an increase in serine palmitoyl transferase. The decrease in cellular diacyglycerol was associated with a 33% decrease in PKCε activation (P < 0.05) and 64% increase in Akt2 phosphorylation (P < 0.05). In summary, Reducing β-catenin expression decreases expression of enzymes involved in hepatic fatty acid esterification, ameliorates hepatic steatosis and lipid-induced insulin resistance.-Popov, V. B., Jornayvaz, F. R., Akgul, E. O., Kanda, S., Jurczak, M. J., Zhang, D., Abudukadier, A., Majumdar, S. K., Guigni, B., Petersen, K. F., Manchem, V. P., Bhanot, S., Shulman, G. I., Samuel, V. T. Second-generation antisense oligonucleotides against β-catenin protect mice against diet-induced hepatic steatosis and hepatic and peripheral insulin resistance. PMID:26644352

  20. Minute virus of mice (MVM) nucleic acid production in susceptible and resistant strains of mice and F1 hybrids.

    PubMed

    Kapil, S

    1995-09-01

    Susceptibility of neonatal mice to the lethal effects of the virulent allotropic variant of minute virus of mice is controlled by host genotype. We quantitated MVM-DNA production in resistant C57BL/6 (B6), susceptible C3H/He (H), and (B6 x H) F1 (F1) hybrid mice. Total DNA extracted from six organs of infected mice on post inoculation days (PID) 3, 5, 7, and 9 was analyzed by dot blot and Southern blot assays. 7 to 100-fold more viral DNA was produced in H mice than in B6 mice on PID 7 depending on the organ and F1 mice phenotypically resembled B6 mice. Southern blot analysis of DNA extracted from infected mice on PID 7 showed a prominent single-stranded band (5 kb, virion DNA) and a faint replicative form (5 kb, double-stranded) in all strains of mice. Total RNA extracted from the organs of B6, H, and F1 mice was analyzed by Northern blot. Viral mRNA production was generally below detection limits. In kidneys, hearts, and intestines of some H mice on PID 7, however, a 1.9 kb transcript was detected, smaller than transcripts for R1, R2 or R3. This study confirms that susceptibility to lethal MVMi infection correlates with upregulation of MVM DNA production, a recessive trait, and perhaps with the production of a novel 1.9 kb transcript. PMID:8549113

  1. Chronic treatment with a carbon monoxide releasing molecule reverses dietary induced obesity in mice

    PubMed Central

    Hosick, Peter A; AlAmodi, Abdulhadi A; Hankins, Michael W; Stec, David E

    2016-01-01

    ABSTRACT Chronic, low level treatment with a carbon monoxide releasing molecule (CO-RM), CORM-A1, has been shown to prevent the development of obesity in response to a high fat diet. The objective of this study was to test the hypothesis that chronic, low level treatment with this CO-RM can reverse established obesity via a mechanism independent of food intake. Dietary induced obese mice were treated with CORM-A1, the inactive compound iCORM-A1, or saline every 48 hours for 30 weeks while maintained on a high fat (60%) diet. Chronic treatment with CORM-A1 resulted in a 33% decrease from initial body weight over the 30 week treatment period while treatment with iCORM and saline were associated with 18 and 25% gain in initial body weight over the same time frame. Chronic treatment with CORM-A1 did not affect food intake or activity but resulted in a significant increase in metabolism. CORM-A1 treatment also resulted in lower fasting blood glucose, improvement in insulin sensitivity and decreased heptatic steatosis. Chronic treatment with CO releasing molecules can reverse dietary induced obesity and normalize insulin resistance independent of changes in food intake or activity. These findings are likely though a mechanism which increases metabolism. PMID:27144091

  2. The Results of Tests of the MICE Spectrometer Solenoids

    SciTech Connect

    Green, Michael A.; Virostek, Steve P.

    2009-10-19

    The Muon Ionization Cooling Experiment (MICE) spectrometer solenoid magnets will be the first magnets to be installed within the MICE cooling channel. The spectrometer magnets are the largest magnets in both mass and surface area within the MICE ooling channel. Like all of the other magnets in MICE, the spectrometer solenoids are kept cold using 1.5 W (at 4.2 K) pulse tube coolers. The MICE spectrometer solenoid is quite possibly the largest magnet that has been cooled using small coolers. Two pectrometer magnets have been built and tested. This report discusses the results of current and cooler tests of both magnets.

  3. Replication of respiratory syncytial virus in lungs of immunodeficient mice

    SciTech Connect

    Wyde, P.R.; Sun, C.S.; Knight, V.

    1983-08-01

    Respiratory syncytial virus was frequently isolated during a 10-day test period from the lungs of 4- to 6-week-old immunodeficient nude (nu/nu) mice and from gamma-irradiated C3H mice inoculated intranasally with this virus, but not from similar aged and comparably inoculated normal littermates of these mice. Virus isolation rates and levels of virus in lungs in both groups of immunodeficient mice were similar. No extrapulmonary dissemination of virus was observed in any test group of mice.

  4. Amphetamine anorexia and hypothalamic catecholamines in genetically obese mice (obob).

    PubMed

    Kuprys, R; Oltmans, G A

    1982-08-01

    Genetically obese mice (obob) and their lean littermates were acclimated to a restricted food-access schedule of six hours and then treated with various doses of amphetamine (0, 3, 5 or 10 mg/kg). Saline-treated obob mice maintained on this schedule retained the primary characteristics of obob mice fed ad lib, i.e., hyperphagia, hyperglycemia, elevated hypothalamic norepinephrine (NE) levels. Both lean and obese mice treated with amphetamine showed a dose-dependent decrease in food intake and hypothalamic NE levels. In obob mice amphetamine treatment reduced food intake and hypothalamic NE levels to values which were not significantly different from those of similarly treated lean mice. When the drug dose was administered on a body weight basis, however, brain amphetamine levels were twice as high in obob as in lean mice. When the amphetamine dose was adjusted to produce approximately equivalent brain levels of amphetamine in obob and lean mice, the obob mice ate significantly more than lean mice. The results indicate that amphetamine is an effective anorectic agent capable of reducing food intake, body weight, and hypothalamic NE levels in obob mice. PMID:7134237

  5. Tempol intake improves inflammatory status in aged mice

    PubMed Central

    Yamato, Mayumi; Ishimatsu, Ayumi; Yamanaka, Yuuki; Mine, Takara; Yamada, Kenichi

    2014-01-01

    Oxidative stress is associated with both healthy aging and age-related disease states. In connection with oxidative stress, immunity is also a major component as a result of the chronic, low-grade inflammation associated with the development of tissue aging. Here we show that long-term treatment with the antioxidant tempol extends life-span in mice. Tempol-treated mice exhibited a reduction in mortality at 20 months. Tempol drinking did not have any effect on body weight, amount of visceral adipose tissue, or plasma biochemical parameters in aged mice. Body temperature of aged control mice (which drank only water) was significantly lower than young mice, but this reduction of body temperature was partially restored in aged mice which drank tempol. Plasma thiobarbituric acid-reactive substances and C-reactive protein were significantly increased in the control aged mice compared with young mice, but levels of both were normalized by tempol drinking. One of the endogenous antioxidants, ascorbic acid, was significantly increased in the plasma of mice which consumed tempol. The proportion of CD4 lymphocytes in the blood of aged tempol-treated mice was partially increased in comparison to aged control mice. These results suggest that the reduction of mortality by tempol is due to amelioration of chronic inflammation and improved function of the immune system through antioxidant effects. PMID:25120275

  6. Chronic stress impairs collateral blood flow recovery in aged mice.

    PubMed

    Lassance-Soares, Roberta M; Sood, Subeena; Chakraborty, Nabarun; Jhamnani, Sunny; Aghili, Nima; Nashin, Hajra; Hammamieh, Rasha; Jett, Marti; Epstein, Stephen E; Burnett, Mary Susan

    2014-11-01

    Chronic stress is associated with increased risk of cardiovascular diseases. Aging is also associated with vascular dysfunction. We hypothesize that chronic stress accelerates collateral dysfunction in old mice. Mice were subjected to either chronic social defeat (CSD) or chronic cold stress (CCS). The CSD mice were housed in a box inside an aggressor's cage and exposed to the aggressor. The CCS group was placed in iced water. After chronic stress, mice underwent femoral artery ligation (FAL) and flow recovery was measured. For the CSD group, appearance and use scores of the foot and a behavioral test were performed. CSD impaired collateral flow recovery after FAL. Further, stressed mice had greater ischemic damage, impaired foot function, and altered behavior. The CCS mice also showed impaired collateral flow recovery. Chronic stress causes hind limb collateral dysfunction in old mice, a conclusion reinforced by the fact that two types of stress produced similar changes. PMID:25315467

  7. Effect of carbon monoxide and nitrogen dioxide on ICR mice

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    Times to incapacitation and death and LC(50) values were determined for male ICR mice exposed to different concentration of carbon monoxide for 30 min and of nitrogen dioxide for 10 min in a 4.2 liter hemispherical chamber. The data indicate that ICR mice are more resistant to these two toxicants than Swiss albino mice. The carbon monoxide LC(50) for a 30-min exposure was about 8,000 ppm for ICR mice compared to 3,570 ppm for Swiss albino mice. The nitrogen dioxide LC(50) for a 10-min exposure was above 2,000 ppm for ICR mice compared to about 1,000 ppm for Swiss albino mice.

  8. The effects of overeating on insulin secretion in normal mice.

    PubMed

    Hasegawa, G; Sawada, M; Nakamura, N; Nakano, K; Kondo, M

    1991-07-01

    This study was performed to examine the effect of overeating on in vivo and in vitro insulin secretion in normal mice. Six week old male CRJ-ICR mice were maintained on a cookie and chocolate mashed diet (C.C. diet) until 30 weeks of age; control mice received an ordinary mouse chow. The mice on the C.C. diet (C.C. mice) consumed 125-130% of the daily caloric intake of control mice throughout the study. C.C. mice developed mild hyperglycemia with relative obesity from 16 weeks of age. Fed blood glucose levels at 30 weeks of age for C.C. mice were 158.3 +/- 6.7 mg/dl as opposed to 127.2 +/- 3.1 mg/dl for controls (p less than 0.01). In experimental mice at 18 weeks of age, plasma insulin response after intraperitoneal glucose load (2 mg/g BW) and insulin secretion at 30 mM glucose from the perfused pancreas were similar to those in control mice. However, at 30 weeks of age, insulin secretion at 30 mM glucose from perfused pancreas in C.C. mice was significantly suppressed compared with that of control mice (p less than 0.02). Conversely, in vivo insulin secretory response to intraperitoneal glucose load was significantly increased in C.C. mice (p less than 0.05). There were no differences in insulin secretion at 15 mM glucose from perfused pancreas. These results indicate that impairment of beta-cell secretory capacity develops in impaired glucose tolerant mice with obesity, while in vivo studies show a high insulin response to glucose. This alteration of beta-cell function may be the initial change during the development of the hyperglycemia-induced defect in insulin secretion. PMID:1841030

  9. Hyperoxia Inhibits T Cell Activation in Mice

    NASA Astrophysics Data System (ADS)

    Hughes-Fulford, M.; Meissler, J.; Aguayo, E. T.; Globus, R.; Aguado, J.; Candelario, T.

    2013-02-01

    Background: The immune response is blunted in mice and humans in spaceflight. The effects of hyperoxia in mice alter expression of some of the same immune response genes. If these two conditions are additive, there could be an increased risk of infection in long duration missions. Immunosuppression is seen in healthy astronauts who have flown in space; however little is known about the mechanisms that cause the reduced immunity in spaceflight. Here we examine the role of oxidative stress on mice exposed to periods of high O2 levels mimicking pre-breathing protocols and extravehicular activity (EVA). To prevent decompression sickness, astronauts are exposed to elevated oxygen (hyperoxia) before and during EVA activities. Spaceflight missions may entail up to 24 hours of EVA per crewmember per week to perform construction and maintenance tasks. The effectiveness and success of these missions depends on designing EVA systems and protocols that maximize human performance and efficiency while minimizing health and safety risks for crewmembers. To our knowledge, no studies have been conducted on the immune system under 100% oxygen exposures to determine the potential for immune compromise due to prolonged and repeated EVAs. Methods: Animals were exposed to hyperoxic or control conditions for 8 hours per day over a period of 3 days, initiated 4 hours into the dark cycle (12h dark/12h light), using animal environmental control cabinets and oxygen controller (Biospherix, Lacona, NY). Experimental mice were exposed to 98-100% oxygen as a model for pre-breathing and EVA conditions, while control mice were maintained in chambers supplied with compressed air. These are ground control studies where we use real-time RTPCR (qRTPCR) to measure gene expression of the early immune gene expression during bead activation of splenocytes of normoxic and hyperoxic mice. All procedures were reviewed and approved by the IACUC at Ames Research Center. After the last 8h of hyperoxic exposure, spleens were removed and the splenocytes were isolated and kept as individual biological samples. We have also examined transcription factors (JASPAR) and pathways of the immune system to help us understand the mechanism of regulation. Results: Our recent mouse immunology experiment aboard STS-131 suggests that the early T cell immune response was inhibited in animals that have been exposed to spaceflight, even 24 hours after return to earth. Moreover, recent experiments in hyperoxic mice show that many of the same genes involved in early T cell activation were altered. Specifically, expression of IL-2Rα, Cxcl2, TNFα, FGF2, LTA and BCL2 genes are dysregulated in mice exposed to hyperoxia. Conclusions: If these hyperoxia-induced changes of gene expression in early T cell activation are additive to the changes seen in the microgravity of spaceflight, there could be an increased infection risk to EVA astronauts, which should be addressed prior to conducting a Mars or other long-term mission.

  10. Methods to measure olfactory behavior in mice

    PubMed Central

    Zou, Junhui; Wang, Wenbin; Pan, Yung-Wei; Lu, Song; Xia, Zhengui

    2015-01-01

    Mice rely on the sense of olfaction to detect food sources, recognize social and mating partners, and avoid predators. Many behaviors of mice including learning and memory, social interaction, fear, and anxiety are closely associated with their function of olfaction, and behavior tasks designed to evaluate those brain functions may use odors as cues. Accurate assessment of olfaction is not only essential for the study of olfactory system but also critical for proper interpretation of various mouse behaviors especially learning and memory, emotionality and affect, and sociality. Here we describe a series of behavior experiments that offer multidimensional and quantitative assessments for mouse’s olfactory function, including olfactory habituation, discrimination, odor preference, odor detection sensitivity, and olfactory memory, to both social and nonsocial odors. PMID:25645244

  11. The detector system of the MICE experiment

    NASA Astrophysics Data System (ADS)

    Orestano, D.

    2010-05-01

    Muon ionization cooling provides the only practical solution to prepare high brilliance beams necessary for a neutrino factory or muon colliders. The muon ionization cooling experiment (MICE) is under development at the Rutherford Appleton Laboratory (UK). It comprises a dedicated beam line to generate a range of input emittance and momentum, with time-of-flight and Cherenkov detectors to ensure a pure muon beam. The emittance is first measured in the upstream magnetic spectrometer with a scintillating fiber tracker. A cooling cell will then follow, alternating energy loss in liquid hydrogen and RF acceleration. A second spectrometer identical to the first one provides a measurement of the outgoing emittance. A particle identification system ensures that the measured muon has not decayed. This paper describes scope and performance of the MICE detector system.

  12. Genetic analysis of litter size in mice

    PubMed Central

    SUTO, Jun-ichi

    2014-01-01

    We performed quantitative trait locus (QTL) mapping analysis for litter size (total number of pups born and/or number of pups born alive) in 255 backcross mice derived from C57BL/6J and RR/Sgn inbred mice. We identified one significant QTL on chromosome 7 and 4 suggestive QTLs on chromosomes 3, 5, 10 and 13. In addition, two suggestive QTLs were identified on chromosomes 1 and 4 for the number of stillbirth. These results suggested that both litter size and number of stillbirth were heritable traits, although they were controlled by distinct genes. The RR allele was associated with reduced litter size and increased stillbirth at all QTLs. Therefore, RR mothers were observed to have reduced prolificacy in this particular genetic cross. PMID:25428703

  13. Human malignant melanoma heterotransplanted to nude mice.

    PubMed

    Tropé, C; Johnsson, J E; Alm, P; Landberg, T; Olsson, H; Wennerberg, J

    1981-01-01

    Five different human malignant melanoma were heterotransplanted subcutaneously to nude mice. When small tissue pieces were used 3 out of 5 tumors grew. Subcutaneous injections of suspended tumor cells were also made, but all failed to take. Metastatic or infiltrative growth was never seen in the mice observed for up to 2.5 months. The successful grafts largely retained the original morphologicaL features. The three successfully transplanted tumors could all be serially transferred with 100% tumor take. In one case passage time was reduced from 40 days to 15 days. As measured with 3H-thymidine incorporation the proliferation rate increased during the passages. These changes might be due to a selection of more rapidly growing tumor cells in the nudes. PMID:7312076

  14. Effects of chronic centrifugation on mice

    NASA Technical Reports Server (NTRS)

    Janer, L.; Duke, J.

    1984-01-01

    Previous studies have shown that exposure to excess gravity in vitro alters the developmental sequence in embryonic mouse limbs and palates (Duke, Janer and Campbell, 1984; Duke, 1983). The effects of excess gravity on in vivo mammalian development was investigated using a small animal centrifuge. Four-week old female mice exposed to excess gravities of 1.8-3.5 G for eight weeks weighed significantly less than controls. Mice were mated after five weeks of adaptation to excess G, and sacrificed either at gestational day 12 or 18. There were fewer pregnancies in the centrifuged group (4/36) than in controls (9/31), and crown rump lengths (CRL) of embryos developing in the centrifuge were less than CRLs of 1-G embryos. These results show that although immersed in amniotic fluid, embryos are responsive to Delta-G.

  15. Construction Noise Decreases Reproductive Efficiency in Mice

    PubMed Central

    Rasmussen, Skye; Glickman, Gary; Norinsky, Rada; Quimby, Fred W; Tolwani, Ravi J

    2009-01-01

    Excessive noise is well known to impair rodent health. To better understand the effect of construction noise and to establish effective noise limits during a planned expansion of our vivarium, we analyzed the effects of construction noise on mouse gestation and neonatal growth. Our hypothesis was that high levels of construction noise would reduce the number of live births and retard neonatal growth. Female Swiss Webster mice were individually implanted with 15 B6CBAF1/J embryos and then exposed to 70- and 90-dBA concrete saw cutting noise samples at defined time points during gestation. In addition, groups of mice with litters were exposed to noise at 70, 80, or 90 dBA for 1 h daily during the first week after parturition. Litter size, birth weight, incidence of stillborn pups, and rate of neonatal weight gain were analyzed. Noise decreased reproductive efficiency by decreasing live birth rates and increasing the number of stillborn pups. PMID:19653943

  16. [Pulmonary calcification in C3H mice].

    PubMed

    Yoshida, M; Uchida, K; Shigemura, M; Fujiwara, H; Kusano, N

    1985-10-01

    C3H mice including aged retired breeding females, aged virginal females, young virginal females and young males were examined for the incidence and severity of pulmonary calcification. Pulmonary calcification appeared in aged females, but not in young mice of either sex, and the lesions in aged breeders were more severe and frequent than in aged virgins. These results indicate that spontaneous pulmonary calcification is observed in aged females of the C3H strain. The findings of increased incidence and severity of pulmonary lesions in aged breeders suggest that pregnancy, delivery and lactation are important enhancing factors. Calcified lesions were also observed in kidney, heart, brain, ovary, choroid plexus, cornea and artery in the animals examined. PMID:4085573

  17. Gene expression: RNA interference in adult mice

    NASA Astrophysics Data System (ADS)

    McCaffrey, Anton P.; Meuse, Leonard; Pham, Thu-Thao T.; Conklin, Douglas S.; Hannon, Gregory J.; Kay, Mark A.

    2002-07-01

    RNA interference is an evolutionarily conserved surveillance mechanism that responds to double-stranded RNA by sequence-specific silencing of homologous genes. Here we show that transgene expression can be suppressed in adult mice by synthetic small interfering RNAs and by small-hairpin RNAs transcribed in vivo from DNA templates. We also show the therapeutic potential of this technique by demonstrating effective targeting of a sequence from hepatitis C virus by RNA interference in vivo.

  18. B cell lymphoma in hiv transgenic mice

    PubMed Central

    2013-01-01

    Background Human Immunodeficiency Virus Type I (HIV-1) infection is associated with a high incidence of B-cell lymphomas. The role of HIV in these lymphomas is unclear and currently there are no valid in vivo models for better understanding HIV-related lymphomagenesis. Transgenic (Tg) 26 mice have a 7.4-kb pNL4-3 HIV-1 provirus lacking a 3.1-kb sequence encompassing parts of the gag-pol region. Approximately 15% of these HIV Tg mice spontaneously develop lymphoma with hallmark pre-diagnostic markers including skin lesions, diffuse lymphadenopathy and an increase in pro-inflammatory serum cytokines. Here we describe the phenotypic and molecular characteristics of the B cell leukemia/lymphoma in the Tg mice. Results The transformed B cell population consists of CD19+pre-BCR+CD127+CD43+CD93+ precursor B cells. The tumor cells are clonal and characterized by an increased expression of several cellular oncogenes. Expression of B cell-stimulatory cytokines IL-1β, IL-6, IL-10, IL-12p40, IL-13 and TNFα and HIV proteins p17, gp120 and nef were elevated in the Tg mice with lymphoma. Conclusions Increased expression of HIV proteins and the B-cell stimulatory factors is consistent with the interpretation that one or more of these factors play a role in lymphoma development. The lymphomas share many similarities with those occurring in HIV/AIDS+ patients and may provide a valuable model for understanding AIDS-related lymphomagenesis and elucidating the role played by HIV-1. PMID:23985023

  19. Health Evaluation of Experimental Laboratory Mice

    PubMed Central

    Burkholder, Tanya; Foltz, Charmaine; Karlsson, Eleanor; Linton, C Garry; Smith, Joanne M

    2012-01-01

    Good science and good animal care go hand in hand. A sick or distressed animal does not produce the reliable results that a healthy and unstressed animal produces. This unit describes the essentials of assessing mouse health, colony health surveillance, common conditions, and determination of appropriate endpoints. Understanding the health and well-being of the mice used in research enables the investigator to optimize research results and animal care. PMID:22822473

  20. Cardiac hypertrophy in mice expressing unphosphorylatable phospholemman

    PubMed Central

    Boguslavskyi, Andrii; Pavlovic, Davor; Aughton, Karen; Clark, James E.; Howie, Jacqueline; Fuller, William; Shattock, Michael J.

    2014-01-01

    Aims Elevation of intracellular Na in the failing myocardium contributes to contractile dysfunction, the negative force–frequency relationship, and arrhythmias. Although phospholemman (PLM) is recognized to form the link between signalling pathways and Na/K pump activity, the possibility that defects in its regulation contribute to elevation of intracellular Na has not been investigated. Our aim was to test the hypothesis that the prevention of PLM phosphorylation in a PLM3SA knock-in mouse (in which PLM has been rendered unphosphorylatable) will exacerbate cardiac hypertrophy and cellular Na overload. Testing this hypothesis should determine whether changes in PLM phosphorylation are simply bystander effects or are causally involved in disease progression. Methods and results In wild-type (WT) mice, aortic constriction resulted in hypophosphorylation of PLM with no change in Na/K pump expression. This under-phosphorylation of PLM occurred at 3 days post-banding and was associated with a progressive decline in Na/K pump current and elevation of [Na]i. Echocardiography, morphometry, and pressure-volume (PV) catheterization confirmed remodelling, dilation, and contractile dysfunction, respectively. In PLM3SA mice, expression of Na/K ATPase was increased and PLM decreased such that net Na/K pump current under quiescent conditions was unchanged (cf. WT myocytes); [Na+]i was increased and forward-mode Na/Ca exchanger was reduced in paced PLM3SA myocytes. Cardiac hypertrophy and Na/K pump inhibition were significantly exacerbated in banded PLM3SA mice compared with banded WT. Conclusions Decreased phosphorylation of PLM reduces Na/K pump activity and exacerbates Na overload, contractile dysfunction, and adverse remodelling following aortic constriction in mice. This suggests a novel therapeutic target for the treatment of heart failure. PMID:25103111

  1. Radioprotectors and Tumors: Molecular Studies in Mice

    SciTech Connect

    Gayle Woloschak, David Grdina

    2010-03-10

    This proposal investigated effects of radiation using a set of archival tissues. Main interests of this proposal were to investigate effects of irradiation alone or in the presence or radioprotectors; to investigate these effects on different tissues; and to use/develop molecular biology techniques that would be suitable for work with archived tissues. This work resulted in several manuscripts published or in preparation. Approach for evaluation of gene copy numbers by quantitative real time PCR has been developed and we are striving to establish methods to utilize Q-RT-PCR data to evaluate genomic instability caused by irradiation(s) and accompanying treatments. References: 1. Paunesku D, Paunesku T, Wahl A, Kataoka Y, Murley J, Grdina DJ, Woloschak GE. Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine. Int J Radiat Biol. 2008, 84(8):623-34. PMID: 18661379, http://informahealthcare.com/doi/full/10.1080/09553000802241762?cookieSet=1 2. Wang Q, Paunesku T and Woloschak GE. Tissue and data archives from irradiation experiments conducted at Argonne National Laboratory over a period of four decades, in press in Radiation and Environmental Biophysics. 3. Alcantara M, Paunesku D, Rademaker A, Paunesku T and Woloschak GE. A RETROSPECTIVE ANALYSIS OF TISSUE TOXICITIES IN B6CF1 MICE IRRADIATED WITH FISSION NEUTRONS OR COBALT 60 GAMMA RAYS: Gender modulates accumulation of tissue toxicities caused by low dose rate fractionated irradiation; in preparation; this document has been uploaded as STI product 4. Wang Q, Paunesku T Wanzer B and Woloschak GE. Mitochondrial gene copy number differences in different tissues of irradiated and control mice with lymphoid cancers; in preparation 5. Wang Q, Raha, S, Paunesku T and Woloschak GE. Evaluation of gene copy number differences in different tissues of irradiated and control mice; in preparation

  2. Trypanosomiasis in mice with naturally occurring immunodeficiencies.

    PubMed Central

    Jones, J F; Hancock, G E

    1983-01-01

    By using mice with naturally occurring defects, we have shown that an intact macrophage system is crucial to survival with the pathogenic protozoan Trypanosoma rhodesiense, since a defect in these cells decreased survival by half. Deficiencies in natural killer cell function or complement levels had no effect on survival. However, the capacity to survive trypanosomiasis was not related to the levels of parasitemia achieved during infection. PMID:6605927

  3. MICE data handling on the Grid

    NASA Astrophysics Data System (ADS)

    Martyniak, J.; Mice Collaboration

    2014-06-01

    The international Muon Ionisation Cooling Experiment (MICE) is designed to demonstrate the principle of muon ionisation cooling for the first time, for application to a future Neutrino factory or Muon Collider. The experiment is currently under construction at the ISIS synchrotron at the Rutherford Appleton Laboratory (RAL), UK. In this paper we present a system - the Raw Data Mover, which allows us to store and distribute MICE raw data - and a framework for offline reconstruction and data management. The aim of the Raw Data Mover is to upload raw data files onto a safe tape storage as soon as the data have been written out by the DAQ system and marked as ready to be uploaded. Internal integrity of the files is verified and they are uploaded to the RAL Tier-1 Castor Storage Element (SE) and placed on two tapes for redundancy. We also make another copy at a separate disk-based SE at this stage to make it easier for users to access data quickly. Both copies are check-summed and the replicas are registered with an instance of the LCG File Catalog (LFC). On success a record with basic file properties is added to the MICE Metadata DB. The reconstruction process is triggered by new raw data records filled in by the mover system described above. Off-line reconstruction jobs for new raw files are submitted to RAL Tier-1 and the output is stored on tape. Batch reprocessing is done at multiple MICE enabled Grid sites and output files are shipped to central tape or disk storage at RAL using a custom File Transfer Controller.

  4. Tetrabenazine is neuroprotective in Huntington's disease mice

    PubMed Central

    2010-01-01

    Background Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in Huntingtin protein (Htt). PolyQ expansion in Httexp causes selective degeneration of striatal medium spiny neurons (MSN) in HD patients. A number of previous studies suggested that dopamine signaling plays an important role in HD pathogenesis. A specific inhibitor of vesicular monoamine transporter (VMAT2) tetrabenazine (TBZ) has been recently approved by Food and Drug Administration for treatment of HD patients in the USA. TBZ acts by reducing dopaminergic input to the striatum. Results In previous studies we demonstrated that long-term feeding with TBZ (combined with L-Dopa) alleviated the motor deficits and reduced the striatal neuronal loss in the yeast artificial chromosome transgenic mouse model of HD (YAC128 mice). To further investigate a potential beneficial effects of TBZ for HD treatment, we here repeated TBZ evaluation in YAC128 mice starting TBZ treatment at 2 months of age ("early" TBZ group) and at 6 months of age ("late" TBZ group). In agreement with our previous studies, we found that both "early" and "late" TBZ treatments alleviated motor deficits and reduced striatal cell loss in YAC128 mice. In addition, we have been able to recapitulate and quantify depression-like symptoms in TBZ-treated mice, reminiscent of common side effects observed in HD patients taking TBZ. Conclusions Our results further support therapeutic value of TBZ for treatment of HD but also highlight the need to develop more specific dopamine antagonists which are less prone to side-effects. PMID:20420689

  5. Microangiography in Living Mice Using Synchrotron Radiation

    SciTech Connect

    Yuan Falei; Wang Yongting; Xie Bohua; Tang Yaohui; Guan Yongjing; Lu Haiyan; Yang Guoyuan; Xie Honglan; Du Guohao; Xiao Tiqiao

    2010-07-23

    Traditionally, there are no methods available to detect the fine morphologic changes of cerebrovasculature in small living animals such as rats and mice. Newly developed synchrotron radiation microangiography can achieve a fine resolution of several micrometers and had provided us with a powerful tool to study the cerebral vasculature in small animals. The purpose of this study is to identify the morphology of cerebrovasculature especially the structure of Lenticulostriate arteries (LSAs) in living mice using the synchrotron radiation source at Shanghai Synchrotron Radiation Facility (SSRF) in Shanghai, China. Adult CD-1 mice weighing 35-40 grams were anesthetized. Nonionic iodine (Omnipaque, 350 mg I /mL) was used as a contrast agent. The study was performed at the BL13W1 beam line at SSRF. The beam line was derived from a storage ring of electrons with an accelerated energy of 3.5 GeV and an average beam current of 200 mA. X-ray energy of 33.3 keV was used to produce the highest contrast image. Images were acquired every 172 ms by a x-ray camera (Photonic-Science VHR 1.38) with a resolution of 13 {mu}m/pixel. The optimal dose of contrast agent is 100 {mu}l per injection and the injecting rate is 33 {mu}l/sec. The best position for imaging is to have the mouse lay on its right or left side, with ventral side facing the X-ray source. We observed the lenticulostriate artery for the first time in living mice. Our result show that there are 4 to 5 lenticulostriate branches originating from the root of middle cerebral artery in each hemisphere. LSAs have an average diameter of 43{+-}6.8 {mu}m. There were no differences between LSAs from the left and right hemisphere (p<0.05). These results suggest that synchrotron radiation may provide a unique tool for experimental stroke research.

  6. The mesenchymal stem cells derived from transgenic mice carrying human coagulation factor VIII can correct phenotype in hemophilia A mice.

    PubMed

    Wang, Qing; Gong, Xiuli; Gong, Zhijuan; Ren, Xiaoyie; Ren, Zhaorui; Huang, Shuzhen; Zeng, Yitao

    2013-12-20

    Hemophilia A (HA) is an inherited X-linked recessive bleeding disorder caused by coagulant factor VIII (FVIII) deficiency. Previous studies showed that introduction of mesenchymal stem cells (MSCs) modified by FVIII-expressing retrovirus may result in phenotypic correction of HA animals. This study aimed at the investigation of an alternative gene therapy strategy that may lead to sustained FVIII transgene expression in HA mice. B-domain-deleted human FVIII (hFVIIIBD) vector was microinjected into single-cell embryos of wild-type mice to generate a transgenic mouse line, from which hFVIIIBD-MSCs were isolated, followed by transplantation into HA mice. RT-PCR and real-time PCR analysis demonstrated the expression of hFVIIIBD in multi-organs of recipient HA mice. Immunohistochemistry showed the presence of hFVIIIBD positive staining in multi-organs of recipient HA mice. ELISA indicated that plasma hFVIIIBD level in recipient mice reached its peak (77 ng/mL) at the 3rd week after implantation, and achieved sustained expression during the 5-week observation period. Plasma FVIII activities of recipient HA mice increased from 0% to 32% after hFVIIIBD-MSCs transplantation. APTT (activated partial thromboplastin time) value decreased in hFVIIIBD-MSCs transplanted HA mice compared with untreated HA mice (45.5 s vs. 91.3 s). Our study demonstrated an effective phenotypic correction in HA mice using genetically modified MSCs from hFVIIIBD transgenic mice. PMID:24377868

  7. Cryptosporidium infections in inbred strains of mice.

    PubMed

    Enriquez, F J; Sterling, C R

    1991-01-01

    Cryptosporidium, a protozoan parasite of man and animals, is an important etiological agent of diarrhea throughout the world, particularly in children and immunocompromised individuals such as AIDS patients. Unfortunately, because of the lack of both in vivo laboratory models and reliable in vitro parasite culture systems, virtually nothing is known about the immunological events occurring during disease. In order to identify reliable animal models for infection, we studied C. parvum infections in 19 different strains of mice representing 12 H-2 haplotypes: A/J, AKR/J, B10.D2/J, B10.M/J, C3H/HeJ, C57BL/65, C57BL/6J-bgJ, CBA/NJ, DBA/1J, DBA/2J, HRS/J, HTG/J, NZB/B1NJ, NZW/J, P/J, RIII/J, SJL/J, SWR/J, and WB/ReJ, and in one gerbil: Meriones unguiculatus. Fecal samples and histological sections of the intestine taken on day 7 post-Cryptosporidium inoculation indicated that only the beige mouse (C57BL/6J-bgJ) harbored significant numbers of parasites compared to the other strains. The numbers of parasites harbored in these NK cell-deficient beige mice were, however, considerably lower than those seen in neonatal mice. Adult inbred mouse strains susceptible to Cryptosporidium infections are discussed. PMID:1818124

  8. Gene Targeting in Mice: a Review

    PubMed Central

    Bouabe, Hicham; Okkenhaug, Klaus

    2015-01-01

    Summary The ability to introduce DNA sequences (e.g. genes) of interest into the germline genome has rendered the mouse a powerful and indispensable experimental model in fundamental and medical research. The DNA sequences can be integrated into the genome randomly or into a specific locus by homologous recombination, in order to: (i) delete or insert mutations into genes of interest to determine their function, (ii) introduce human genes into the genome of mice to generate animal models enabling study of human-specific genes and diseases, e.g. mice susceptible to infections by human-specific pathogens of interest, (iii) introduce individual genes or genomes of pathogens (such as viruses) in order to examine the contributions of such genes to the pathogenesis of the parent pathogens, (iv) and last but not least introduce reporter genes that allow monitoring in vivo or ex vivo the expression of genes of interest. Furthermore, the use of recombination systems, such as Cre/loxP or FRT/FLP, enables conditional induction or suppression of gene expression of interest in a restricted period of mouse’s lifetime, in a particular cell type, or in a specific tissue. In this review, we will give an updated summary of the gene targeting technology and discuss some important considerations in the design of gene-targeted mice. PMID:23996268

  9. Novel transcranial magnetic stimulation coil for mice

    NASA Astrophysics Data System (ADS)

    March, Stephen; Stark, Spencer; Crowther, Lawrence; Hadimani, Ravi; Jiles, David

    2014-03-01

    Transcranial magnetic stimulation (TMS) shows potential for non-invasive treatment of various neurological disorders. Significant work has been performed on the design of coils used for TMS on human subjects but few reports have been made on the design of coils for use on the brains of animals such as mice. This work is needed as TMS studies utilizing mice can allow rapid preclinical development of TMS for human disorders but the coil designs developed for use on humans are inadequate for optimal stimulation of the much smaller mouse brain. A novel TMS coil has been developed with the goal of inducing strong and focused electric fields for the stimulation of small animals such as mice. Calculations of induced electric fields were performed utilizing an MRI derived inhomogeneous model of an adult male mouse. Mechanical and thermal analysis of this new TMS helmet-coil design have also been performed at anticipated TMS operating conditions to ensure mechanical stability of the new coil and establish expected linear attraction and rotational force values. Calculated temperature increases for typical stimulation periods indicate the helmet-coil system is capable of operating within established medical standards. A prototype of the coil has been fabricated and characterization results are presented.

  10. Critical period for acoustic preference in mice

    PubMed Central

    Yang, Eun-Jin; Lin, Eric W.; Hensch, Takao K.

    2012-01-01

    Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a “critical period” for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their innate bias for silent shelter, which typically could not be altered in adulthood. Instead, exposing adult mice treated acutely with valproic acid or carrying a targeted deletion of the Nogo receptor (NgR−/−) unmasked a strong plasticity of preference consistent with a reopening of the critical period as seen in other systems. Imaging of cFos expression revealed a prominent neuronal activation in response to the exposed music in the prelimbic and infralimbic medial prefrontal cortex only under conditions of open plasticity. Neither behavioral changes nor selective medial prefrontal cortex activation was observed in response to pure tone exposure, indicating a music-specific effect. Open-field center crossings were increased concomitant with shifts in music preference, suggesting a potential anxiolytic effect. Thus, music may offer both a unique window into the emotional state of mice and a potentially efficient assay for molecular “brakes” on critical period plasticity common to sensory and higher order brain areas. PMID:23045690

  11. Parturition failure in mice lacking Mamld1

    PubMed Central

    Miyado, Mami; Miyado, Kenji; Katsumi, Momori; Saito, Kazuki; Nakamura, Akihiro; Shihara, Daizou; Ogata, Tsutomu; Fukami, Maki

    2015-01-01

    In mice, the onset of parturition is triggered by a rapid decline in circulating progesterone. Progesterone withdrawal occurs as a result of functional luteolysis, which is characterized by an increase in the enzymatic activity of 20α-hydroxysteroid dehydrogenase (20α-HSD) in the corpus luteum and is mediated by the prostaglandin F2α (PGF2α) signaling. Here, we report that the genetic knockout (KO) of Mamld1, which encodes a putative non-DNA-binding regulator of testicular steroidogenesis, caused defective functional luteolysis and subsequent parturition failure and neonatal deaths. Progesterone receptor inhibition induced the onset of parturition in pregnant KO mice, and MAMLD1 regulated the expression of Akr1c18, the gene encoding 20α-HSD, in cultured cells. Ovaries of KO mice at late gestation were morphologically unremarkable; however, Akr1c18 expression was reduced and expression of its suppressor Stat5b was markedly increased. Several other genes including Prlr, Cyp19a1, Oxtr, and Lgals3 were also dysregulated in the KO ovaries, whereas PGF2α signaling genes remained unaffected. These results highlight the role of MAMLD1 in labour initiation. MAMLD1 likely participates in functional luteolysis by regulating Stat5b and other genes, independent of the PGF2α signaling pathway. PMID:26435405

  12. Antifatigue effect of Gracilaria eucheumoides in mice

    PubMed Central

    SHAO, JIN-TING; WANG, MEI-YAN; ZHENG, LU-BIN

    2013-01-01

    Gracilaria eucheumoides Linn (Gracilariaceae; G. eucheumoides) is abundant in dietary fiber, which aids the clearance of excess cholesterol from the blood and maintains stable blood glucose levels. The aim of the present study was to investigate the antifatigue effect of G. eucheumoides in mice and the physiological and molecular mechanisms underlying this effect. Mice were randomly divided into four groups and three of the groups were administered different doses of G. eucheumoides extract. A loaded swimming test demonstrated that the swimming times of the low-, medium- and high-dose groups were longer than those of the control group. Examinations revealed that the liver and muscle glycogen, lactate dehydrogenase and blood glucose concentration levels of the treatment groups were higher than those of the control group (P<0.05). However, this was not the case for lactic acid concentration (P>0.05). Quantitative polymerase chain reaction showed that the gene expression levels of glucose transport protein 4 and AMP-activated protein kinase in the medium-dose group exhibited the largest increases, compared with the other treatment groups, and were 3.0- and 1.8-fold higher than those in the control group, respectively. The results of the present study indicated that G. eucheumoides exerts an antifatigue effect on mice. PMID:24255683

  13. Resveratrol alleviates alcoholic fatty liver in mice

    PubMed Central

    Ajmo, Joanne M.; Liang, Xiaomei; Rogers, Christopher Q.; Pennock, Brandi; You, Min

    2008-01-01

    Alcoholic fatty liver is associated with inhibition of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), two critical signaling molecules regulating the pathways of hepatic lipid metabolism in animals. Resveratrol, a dietary polyphenol, has been identified as a potent activator for both SIRT1 and AMPK. In the present study, we have carried out in vivo animal experiments that test the ability of resveratrol to reverse the inhibitory effects of chronic ethanol feeding on hepatic SIRT1-AMPK signaling system and to prevent the development of alcoholic liver steatosis. Resveratrol treatment increased SIRT1 expression levels and stimulated AMPK activity in livers of ethanol-fed mice. The resveratrol-mediated increase in activities of SIRT1 and AMPK was associated with suppression of sterol regulatory element binding protein 1 (SREBP-1) and activation of peroxisome proliferator-activated receptor γ coactivator α (PGC-1α). In parallel, in ethanol-fed mice, resveratrol administration markedly increased circulating adiponectin levels and enhanced mRNA expression of hepatic adiponectin receptors (AdipoR1/R2). In conclusion, resveratrol treatment led to reduced lipid synthesis and increased rates of fatty acid oxidation and prevented alcoholic liver steatosis. The protective action of resveratrol is in whole or in part mediated through the upregulation of a SIRT1-AMPK signaling system in the livers of ethanol-fed mice. Our study suggests that resveratrol may serve as a promising agent for preventing or treating human alcoholic fatty liver disease. PMID:18755807

  14. Intralymphatic Immunotherapy and Vaccination in Mice

    PubMed Central

    Johansen, Pål; Kündig, Thomas M.

    2014-01-01

    Vaccines are typically injected subcutaneously or intramuscularly for stimulation of immune responses. The success of this requires efficient drainage of vaccine to lymph nodes where antigen presenting cells can interact with lymphocytes for generation of the wanted immune responses. The strength and the type of immune responses induced also depend on the density or frequency of interactions as well as the microenvironment, especially the content of cytokines. As only a minute fraction of peripherally injected vaccines reaches the lymph nodes, vaccinations of mice and humans were performed by direct injection of vaccine into inguinal lymph nodes, i.e. intralymphatic injection. In man, the procedure is guided by ultrasound. In mice, a small (5-10 mm) incision is made in the inguinal region of anesthetized animals, the lymph node is localized and immobilized with forceps, and a volume of 10-20 μl of the vaccine is injected under visual control. The incision is closed with a single stitch using surgical sutures. Mice were vaccinated with plasmid DNA, RNA, peptide, protein, particles, and bacteria as well as adjuvants, and strong improvement of immune responses against all type of vaccines was observed. The intralymphatic method of vaccination is especially appropriate in situations where conventional vaccination produces insufficient immunity or where the amount of available vaccine is limited. PMID:24513675

  15. Dietary effect on immunological energetics in mice.

    PubMed

    Martel, Sebastin I; Riquelme, Sebastin A; Kalergis, Alexis M; Bozinovic, Francisco

    2014-10-01

    Defense against natural aggressors, such as bacterial infections, requires both energy and an immune-cellular response. However, the question as to how these two components are interconnected in small endotherms by means of the host diet remains only poorly understood. Here, we tested in laboratory mice whether dietary proteins and carbohydrates can modulate the interplay between energy expenditure, food intake and the innate and adaptive immune response when confronting a bacterial challenge (Bacillus Calmette-Gurin, BCG). We observed that mice fed with a high protein diet (HP) developed a better immune response associated to increased numbers of circulating monocytes. In addition, HP diet directly influenced the peripheral blood proportions of both T and B lymphocytes even before the BCG challenge. Interestingly, animals that developed this type of immune response after BCG challenge showed an increased rate of metabolism and food consumption before being challenged. Thus, HP diet induced in non-challenged animals a similar energy expenditure and food intake described by BCG-treated mice. These data suggest that a high amount of proteins in diet can modify the energetic and nutrient dynamic in the host causing a better immune reaction against a microbial challenge. PMID:25129229

  16. Heart regeneration in adult MRL mice

    NASA Astrophysics Data System (ADS)

    Leferovich, John M.; Bedelbaeva, Khamilia; Samulewicz, Stefan; Zhang, Xiang-Ming; Zwas, Donna; Lankford, Edward B.; Heber-Katz, Ellen

    2001-08-01

    The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary capacity to heal surgical wounds, a complex trait that maps to at least seven genetic loci. Here, we extend these studies to cardiac wounds and demonstrate that a severe transmural, cryogenically induced infarction of the right ventricle heals extensively within 60 days, with the restoration of normal myocardium and function. Scarring is markedly reduced in MRL mice compared with C57BL/6 mice, consistent with both the reduced hydroxyproline levels seen after injury and an elevated cardiomyocyte mitotic index of 10-20% for the MRL compared with 1-3% for the C57BL/6. The myocardial response to injury observed in these mice resembles the regenerative process seen in amphibians.

  17. Splenic Marginal Zone Lymphomas of Mice

    PubMed Central

    Fredrickson, Torgny N.; Lennert, Karl; Chattopadhyay, Sisir K.; Morse, Herbert C.; Hartley, Janet W.

    1999-01-01

    Splenic marginal zone lymphomas (MZLs) have been found to occur at a high frequency in NFS.N mice congenic for high-expressing ecotropic murine leukemia virus (MuLV) genes from AKR and C58 mice. Based on morphological, immunological, and molecular studies of these mice, MZL is clearly recognizable as a distinct disease with a characteristic clinical behavior. MZL was staged according to the degree of accumulation and morphological change of cells within the splenic marginal zone, as follows: 1) a moderate increase in normal-looking MZ cells, judged to be prelymphomatous, and 2) MZL in three variants: i) distinct enlargement of MZ by normal-looking cells (MZL), ii) distinct enlargement of MZ by basophilic centroblast-like cells (MZL+), and iii) extensive splenic involvement by centroblast-like cells (MZL++). The rate of mitosis and apoptosis increases with lymphoma grade. In most cases, emergence of a dominant IgH clonal pattern in paired splenic biopsy and necropsy samples was correlated with progression. MZLs were transplantable and homed to the spleen. MZL may constitute a commonly occurring lymphoma type unrecognized, in part, because of the centroblastic morphology of high-grade MZL and possible overgrowth of lower-grade MZL by more aggressive follicular lymphomas. PMID:10079258

  18. Olfactory epithelium changes in germfree mice

    PubMed Central

    François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

    2016-01-01

    Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

  19. How do mice follow odor trails?

    NASA Astrophysics Data System (ADS)

    Zwicker, David; Trastour, Sophie; Mishra, Shruti; Mathis, Alexander; Murthy, Venkatesh; Brenner, Michael P.

    2015-11-01

    Mice are excellent at following odor trails e.g. to locate food or to find mates. However, it is not yet understood what navigation strategies they use. In principle, they could either evaluate temporal differences between sniffs or they could use concurrent input from the two nostrils. It is unknown to what extend these two strategies contribute to mice's performance. When mice follow trails, odors evaporate from the ground, are transported by flow in the air, and are then inhaled with the two nostrils. In order to differentiate between the two navigation strategies, we determine what information the mouse receives: first, we calculate the airflow by numerically solving the incompressible Navier-Stokes equations. We then determine the spatiotemporal odor concentration from the resulting advection-diffusion equations. Lastly, we determine the odor amount in each nostril by calculating the inhalation volumes using potential flow theory. Taken together, we determine the odor amount in each nostril during each sniff, allowing a detailed study of navigation strategies.

  20. Zoopharmacognosy in Diseased Laboratory Mice: Conflicting Evidence

    PubMed Central

    Kapadia, Minesh; Zhao, Hui; Ma, Donglai; Hatkar, Rupal; Marchese, Monica; Sakic, Boris

    2014-01-01

    Zoopharmacognosy denotes a constellation of learned ingestive responses that promote healing and survival of infected or poisoned animals. A similar self-medication phenomenon was reported in diseased laboratory rodents. In particular, a series of studies revealed that autoimmune MRL/lpr mice readily consume solutions paired or laced with cyclophosphamide (CY), an immunosuppressive drug that prevents inflammatory damage to internal organs. However, due to design limitations, it could not be elucidated whether such a response reflects the learned therapeutic effect of CY, or a deficit in sensory input. We presently assess the behavioural effects of prolonged consumption of CY-laced, 16% sucrose solution in a continuous choice paradigm, with tap water available ad lib. Contrary to overall expectation, MRL/lpr mice did not increase their intake of CY with disease progression. Moreover, they ingested lower doses of CY and preferred less CY-laced sucrose solution than age-matched controls. The results obtained could not confirm zoopharmacognosy in diseased MRL/lpr mice, likely due to impaired responsiveness to palatable stimulation, or attenuated survival mechanisms after prolonged inbreeding in captivity. However, by revealing the effectiveness of unrestricted drinking of drug-laced sucrose solution on behavior and immunity, the current study supports broader use of such an administration route in behavioural studies sensitive to external stressors. PMID:24956477

  1. Olfactory epithelium changes in germfree mice.

    PubMed

    François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

    2016-01-01

    Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

  2. Superconducting solenoids for the MICE channel

    SciTech Connect

    Green, M.A.; Barr, G.; Baynham, D.E.; Rockford, J.H.; Fabbricatore, P.; Farinin, S.; Palmer, R.B.; Rey, J.M.

    2003-05-01

    This report describes the channel of superconductingsolenoids for the proposed international Muon Ionization CoolingExperiment (MICE). MICE consists of two cells of a SFOFO cooling channelthat is similar to that studied in the level 2 study of a neutrinofactory[1]. MICE also consists of two detector solenoids at either end ofthe cooling channel section. The superconducting solenoids for MICEperform three functions. The coupling solenoids, which are largesolenoids around 201.25 MHz RF cavities, couple the muon beam between thefocusing sections as it passes along the cooling channel. The focusingsolenoids are around the liquid hydrogen absorber that reduces themomentum of the muons in all directions. These solenoids generate agradient field along the axis as they reduce the beta of the muon beambefore it enters the absorber. Each detector solenoid system consists offive coils that match the muon beam coming to or from an absorber to a4.0 T uniform solenoidal field section that that contains the particledetectors at the ends of the experiment. There are detector solenoids atthe beginning and at the end of the experiment. This report describes theparameters of the eighteen superconducting coils that make up the MICEmagnetic channel.

  3. Of mice and (Viking?) men: phylogeography of British and Irish house mice.

    PubMed

    Searle, Jeremy B; Jones, Catherine S; Gündüz, Islam; Scascitelli, Moira; Jones, Eleanor P; Herman, Jeremy S; Rambau, R Victor; Noble, Leslie R; Berry, R J; Giménez, Mabel D; Jóhannesdóttir, Fríoa

    2009-01-22

    The west European subspecies of house mouse (Mus musculus domesticus) has gained much of its current widespread distribution through commensalism with humans. This means that the phylogeography of M. m. domesticus should reflect patterns of human movements. We studied restriction fragment length polymorphism (RFLP) and DNA sequence variations in mouse mitochondrial (mt) DNA throughout the British Isles (328 mice from 105 localities, including previously published data). There is a major mtDNA lineage revealed by both RFLP and sequence analyses, which is restricted to the northern and western peripheries of the British Isles, and also occurs in Norway. This distribution of the 'Orkney' lineage fits well with the sphere of influence of the Norwegian Vikings and was probably generated through inadvertent transport by them. To form viable populations, house mice would have required large human settlements such as the Norwegian Vikings founded. The other parts of the British Isles (essentially most of mainland Britain) are characterized by house mice with different mtDNA sequences, some of which are also found in Germany, and which probably reflect both Iron Age movements of people and mice and earlier development of large human settlements. MtDNA studies on house mice have the potential to reveal novel aspects of human history. PMID:18826939

  4. ALTEA-MICE: experiment at GSI

    NASA Astrophysics Data System (ADS)

    Rinaldi, A.; Altea-Mice Team

    ALTEA is designed to obtain evidence on the interaction between cosmic radiation and brain function suggested e.g. by the anomalous visual percepts (phosphenes) reported by astronauts. The project will monitor the dynamics of astronauts' brain and retina electrophysiology in concomitance with exposure to cosmic radiation. ALTEA is scheduled to fly in November 2004. ALTEA-MICE experiment supports the ALTEA space experiment with data obtained under controlled conditions in accelerator. Here we describe procedures and preliminary results of the MICE experiment carried out at GSI (Darmstadt, FRG). Sixteen adult mice (including controls) were studied. Each mouse was dark adapted, aligned to the beam line on a holder also maintaining temperature at 360 C, and then exposed to i) series of luminance (white light) stimuli at 0.9 Hz ,ii) to short (˜ 1 ms) bursts of 12C ions at 200 MeV/nucleon delivered at 0.5 - 0.7 Hz , and iii) to luminance stimulation with the stimulus modalities used before radiation. Steps (ii) and (iii) were repeated twice in 3 mice. The pulsed beam radiation was focused on the right eye of each mouse through a collimator. The number of 12C ions ranged across mice from about 5x104 to about 2x106. The absorbed dose varied from few mGy to 102 mGy. Electrophysiological signals were recorded from the retina and visual cortex during (and with time information with) luminance stimulation and beam bursts and analyzed offline. Retinal and cortical responses to luminance were recorded in the accelerator cave with adequate morphologies, amplitudes, latencies from stimulus and reproducibility. Radiation-related changes in the responses to luminance and transient electrophysiological events time locked to particle pulses are studied offline. Ad hoc optimal filtering and epoch selection strategies based on signal characterization are being developed. Significant changes in the retinal response to luminance do not seem to have been induced by irradiation. Results of systematic analyses will be presented at the conference. Further experiments are scheduled in the summer at GSI and NSRL (Brookhaven National Laboratories USA)

  5. Intestinal microbiota modulates gluten-induced immunopathology in humanized mice.

    PubMed

    Galipeau, Heather J; McCarville, Justin L; Huebener, Sina; Litwin, Owen; Meisel, Marlies; Jabri, Bana; Sanz, Yolanda; Murray, Joseph A; Jordana, Manel; Alaedini, Armin; Chirdo, Fernando G; Verdu, Elena F

    2015-11-01

    Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. The recent increase in CD incidence suggests that additional environmental factors, such as intestinal microbiota alterations, are involved in its pathogenesis. However, there is no direct evidence of modulation of gluten-induced immunopathology by the microbiota. We investigated whether specific microbiota compositions influence immune responses to gluten in mice expressing the human DQ8 gene, which confers moderate CD genetic susceptibility. Germ-free mice, clean specific-pathogen-free (SPF) mice colonized with a microbiota devoid of opportunistic pathogens and Proteobacteria, and conventional SPF mice that harbor a complex microbiota that includes opportunistic pathogens were used. Clean SPF mice had attenuated responses to gluten compared to germ-free and conventional SPF mice. Germ-free mice developed increased intraepithelial lymphocytes, markers of intraepithelial lymphocyte cytotoxicity, gliadin-specific antibodies, and a proinflammatory gliadin-specific T-cell response. Antibiotic treatment, leading to Proteobacteria expansion, further enhanced gluten-induced immunopathology in conventional SPF mice. Protection against gluten-induced immunopathology in clean SPF mice was reversed after supplementation with a member of the Proteobacteria phylum, an enteroadherent Escherichia coli isolated from a CD patient. The intestinal microbiota can both positively and negatively modulate gluten-induced immunopathology in mice. In subjects with moderate genetic susceptibility, intestinal microbiota changes may be a factor that increases CD risk. PMID:26456581

  6. Antiorthostatic suspension stimulates profiles of macrophage activation in mice

    NASA Technical Reports Server (NTRS)

    Miller, E. S.; Bates, R. A.; Koebel, D. A.; Sonnenfeld, G.

    1999-01-01

    The antiorthostatic suspension model simulates certain physiological effects of spaceflight. We have previously reported BDF1 mice suspended by the tail in the antiorthostatic orientation for 4 days express high levels of resistance to virulent Listeria monocytogenesinfection. In the present study, we examined whether the increased resistance to this organism correlates with profiles of macrophage activation, given the role of the macrophage in killing this pathogen in vivo. We infected BDF1 mice with a lethal dose of virulent L. monocytogenes on day 4 of antiorthostatic suspension and 24 h later constructed profiles of macrophage activation. Viable listeria could not be detected in mice suspended in the antiorthostatic orientation 24 h after infection. Flow cytometric analysis revealed the numbers of granulocytes and mononuclear phagocytes in the spleen of infected mice were not significantly altered as a result of antiorthostatic suspension. Splenocytes from antiorthostatically suspended infected mice produced increased titers of IL-1. Serum levels of neopterin, a nucleotide metabolite secreted by activated macrophages, were enhanced in mice infected during antiorthostatic suspension, but not in antiorthostatically suspended naive mice. Splenic macrophages from mice infected on day 4 of suspension produced enhanced levels of lysozyme. In contrast to the results from antiorthostatically suspended infected mice, macrophages from antiorthostatically suspended uninfected mice did not express enhanced bactericidal activities. The collective results indicate that antiorthostatic suspension can stimulate profiles of macrophage activation which correlate with increased resistance to infection by certain classes of pathogenic bacteria.

  7. Neuronal Serotonin Regulates Growth of the Intestinal Mucosa in Mice

    PubMed Central

    Gross, Erica R.; Gershon, Michael D.; Margolis, Kara G.; Gertsberg, Zoya V.; Cowles, Robert A.

    2013-01-01

    BACKGROUND & AIMS The enteric abundance of serotonin (5-HT), its ability to promote proliferation of neural precursors, and reports that 5-HT antagonists affect crypt epithelial proliferation led us to investigate whether 5-HT affects growth and maintenance of the intestinal mucosa in mice. METHODS Mice that lack the serotonin re-uptake transporter (SERTKO mice) and wild-type mice were given injections of selective serotonin re-uptake inhibitors (gain-of-function models). We also analyzed mice that lack tryptophan hydroxylase-1 (TPH1KO mice, which lack mucosal but not neuronal 5-HT) and mice deficient in tryptophan hydroxylase-2 (TPH2KO mice, which lack neuronal but not mucosal 5-HT) (loss-of-function models). Wild-type and SERTKO mice were given ketanserin (an antagonist of the 5-HT receptor, 5-HT2A) or scopolamine (an antagonist of the muscarinic receptor). 5-HT2A receptors and choline acetyltransferase were localized by immunocytochemical analysis. RESULTS Growth of the mucosa and proliferation of mucosal cells were significantly greater in SERTKO mice and in mice given selective serotonin reuptake inhibitors than in wild-type mice, but were diminished in TPH2KO (but not in TPH1KO) mice. Ketanserin and scopolamine each prevented the ability of SERT knockout or inhibition to increase mucosal growth and proliferation. Cholinergic submucosal neurons reacted with antibodies against 5-HT2A. CONCLUSIONS 5-HT promotes growth and turnover of the intestinal mucosal epithelium. Surprisingly, these processes appear to be mediated by neuronal, rather than mucosal, 5-HT. The 5-HT2A receptor activates cholinergic neurons, which provide a muscarinic innervation to epithelial effectors. PMID:22609381

  8. Lipid metabolism and body composition in Gclm(-/-) mice

    SciTech Connect

    Kendig, Eric L.; Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 ; Chen, Ying; Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N.; Genter, Mary Beth; Nebert, Daniel W.; Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 ; Shertzer, Howard G.

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial oxygen consumption. Black-Right-Pointing-Pointer Expression of lipid metabolizing genes is extremely low in Gclm(-/-) mice.

  9. Infectivity period of mice inoculated with human adenoviruses

    PubMed Central

    Krishnapuram, Rashmi; Kirk-Ballard, Heather; Zuberi, Aamri; Dhurandhar, Nikhil V

    2016-01-01

    Due to non-productive infections, mice are not a good model to study some human adenoviruses. However, mice provide an excellent model to study the metabolic effects of human adenovirus, Ad36. Research interest in Ad36 is increasing rapidly, and consequently an increase in the use of mice as a model is anticipated. However, little is known about the transmission potential of Ad36 from infected mice to other laboratory animals or personnel. While underestimating the infectivity could promote inadvertent spread of Ad36, overstating it could drain valuable laboratory resources and animals. Therefore, we determined the duration of infectivity in female C57BL/6J mice that were experimentally infected with human adenoviruses Ad36 or Ad2. Other uninfected mice were co-housed for one week with the experimentally-infected animals, four or eight weeks postinfection. Additionally, uninfected mice were housed in the cages of mice that were infected with Ad36, 12 weeks earlier. The presence of viral DNA in tissues was used to indicate infection of mice. Although experimentally-infected mice harboured viral DNA at least up to 12 weeks, the horizontal transmission of infection was observed in co-housed mice only up to four weeks postinfection. Thus, Ad36-infected mice should be considered potentially infective for eight weeks and appropriate handling and barrier containment should be used. After eight week postinfection, horizontal transmission appears unlikely. This information may provide guidelines for animal handling, and experimental design using Ad36, which may increase safety for laboratory personnel and reduce the number of mice required for experiments. PMID:21257643

  10. Prevention of Murine Norovirus Infection in Neonatal Mice by Fostering

    PubMed Central

    Compton, Susan R

    2008-01-01

    Murine norovirus (MNV) causes subclinical chronic infections in adult immunocompetent mice and is endemic in many mouse colonies. The susceptibility of neonatal mice to MNV infection was investigated. Intestinal homogenates from Swiss Webster (SW) mice inoculated orally with MNV-L on postpartum days (ppd) 1 to 3 were negative for MNV by RT-PCR at postinoculation days (pid) 3 and 7. In contrast, 69% of intestinal homogenates prepared on pid 3 and 7 from mice inoculated orally at ppd 5 to 8 were MNV-positive by RT-PCR. Because only mice 10 d of age or older were infected by contact with infected dams, a study was performed to determine whether fostering of neonatal mice from MNV-infected to MNV-naïve dams could be effective at preventing infection of neonatal mice. Four litters each of 1-, 2-, 4-, or 6 d-old mice from MNV-L–infected dams were transferred to naïve dams with similar-aged litters and vice versa. On ppd 21, feces from all MNV-infected dams and litters transferred to them were MNV-positive. In contrast on ppd 21, feces from all MNV-naïve dams and litters transferred to them were MNV-negative. Fostering of 2-d-old mice from 5 of 5 MNV-C–, 5 of 6 MNV-D–, and 7 of 8 MNV-G–infected dams onto MNV-naïve dams prevented MNV infection of the foster mice. In the 2 litters where MNV was detected, dams were infected within 7 d of transfer, suggesting that the neonatal mice had served as fomites. In summary, fostering was effective at preventing MNV infection in 33 of 35 litters of neonatal mice. Precautions to prevent transmission of virus on the surface of neonatal mice to foster dams could increase the efficiency of the fostering process. PMID:18459709

  11. Gradual Elimination of Retroviruses in YBR/Ei Mice

    PubMed Central

    MacDearmid, Cameron C.; Case, Laure K.; Starling, Christa L.; Golovkina, Tatyana V.

    2006-01-01

    Mouse mammary tumor virus (MMTV), a well-characterized retrovirus that causes mammary tumors in susceptible mice, is commonly used to investigate virus-host interactions. We have shown that YBR/Ei mice demonstrate a novel, dominant mechanism of resistance to MMTV infection and MMTV-induced mammary tumors. MMTV can both establish infection in YBR/Ei mice and be transmitted by YBR/Ei mice as an infectious virus. However, virus production is severely attenuated, resulting in gradual clearance of infection in successive generations. Our transfer experiments showed that T cells generated in MMTV-infected resistant mice were required to restrict MMTV replication in susceptible mice. These results emphasize the importance of inducing T-cell responses for effective protection against retroviral infections. PMID:16474128

  12. Molecular detection of murine noroviruses in laboratory and wild mice.

    PubMed

    Farkas, Tibor; Fey, Brittney; Keller, Gary; Martella, Vito; Egyed, Laszlo

    2012-12-01

    Fecal specimens collected from 121 laboratory mice, 30 striped field mice (Apodemus agrarius), 70 yellow-necked mice (Apodemus flavicollis), and 3 bank voles (Myodes glareolus) were tested in sample pools for the presence of murine noroviruses (MNV). Ten of 41 laboratory mice and 2 of 3 striped field mice pooled samples were positive for MNV. All laboratory mouse MNVs were closely related to previously described MNVs. The complete ORF2 (VP1) of both striped field mouse MNVs identified in this study was 1623 nt (541 aa) long and differed at 12% nt (8% aa) positions from each other, at 22-24% nt (15-18% aa) positions from the laboratory mouse MNVs and at 20-22% nt (13-14% aa) positions from the recently described wood mouse (Apodemus sylvaticus) MNVs. This study provides further evidence for the circulation of novel, genetically diverse MNVs in wild mice. PMID:22748629

  13. Neutrophil depletion delays wound repair in aged mice

    PubMed Central

    Nishio, Naomi; Okawa, Yayoi; Sakurai, Hidetoshi

    2008-01-01

    One of the most important clinical problems in caring for elderly patients is treatment of pressure ulcers. One component of normal wound healing is the generation of an inflammatory reaction, which is characterized by the sequential infiltration of neutrophils, macrophages and lymphocytes. Neutrophils migrate early in the wound healing process. In aged C57BL/6 mice, wound healing is relatively inefficient. We examined the effects of neutrophil numbers on wound healing in both young and aged mice. We found that the depletion of neutrophils by anti-Gr-1 antibody dramatically delayed wound healing in aged mice. The depletion of neutrophils in young mice had less effect on the kinetics of wound healing. Intravenous G-CSF injection increased the migration of neutrophils to the wound site. While the rate of wound repair did not change significantly in young mice following G-CSF injection, it increased significantly in old mice. PMID:19424869

  14. Contact hypersensitivity response to isophorone diisocyanate in mice

    SciTech Connect

    Stern, M.L.; Brown, T.A.; Brown, R.D.; Munson, A.E. )

    1989-09-01

    Isophorone diisocyanate was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 0.1, 0.3, and 1.0% isophorone diisocyanate and challenged with 3.0% isophorone diisocyanate. Doses of isophorone diisocyanate were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of complete Freund's adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity responses to isophorone diisocyanate with or without adjuvant pretreatment.

  15. Hindlimb skeletal muscle function in myostatin-deficient mice.

    PubMed

    Gentry, Bettina A; Ferreira, J Andries; Phillips, Charlotte L; Brown, Marybeth

    2011-01-01

    Absence of functional myostatin (MSTN) during fetal development results in adult skeletal muscle hypertrophy and hyperplasia. To more fully characterize MSTN loss in hindlimb muscles, the morphology and contractile function of the soleus, plantaris, gastrocnemius, tibialis anterior, and quadriceps muscles in male and female null (Mstn(-/-)), heterozygous (Mstn(+/-)), and wild-type (Mstn(+/+)) mice were investigated. Muscle weights of Mstn(-/-) mice were greater than those of Mstn(+/+) and Mstn(+/-) mice. Fiber cross-sectional area (CSA) was increased in female Mstn(-/-) soleus and gastrocnemius muscles and in the quadriceps of male Mstn(-/-) mice; peak tetanic force in Mstn(-/-) mice did not parallel the increased muscle weight or CSA. Male Mstn(-/-) muscle exhibited moderate degeneration. Visible pathology in male mice and decreased contractile strength relative to increased muscle weight suggest MSTN loss results in muscle impairment, which is dose-, sex-, and muscle-dependent. PMID:21082689

  16. Knockout of Foxp2 disrupts vocal development in mice.

    PubMed

    Castellucci, Gregg A; McGinley, Matthew J; McCormick, David A

    2016-01-01

    The FOXP2 gene is important for the development of proper speech motor control in humans. However, the role of the gene in general vocal behavior in other mammals, including mice, is unclear. Here, we track the vocal development of Foxp2 heterozygous knockout (Foxp2+/-) mice and their wildtype (WT) littermates from juvenile to adult ages, and observe severe abnormalities in the courtship song of Foxp2+/- mice. In comparison to their WT littermates, Foxp2+/- mice vocalized less, produced shorter syllable sequences, and possessed an abnormal syllable inventory. In addition, Foxp2+/- song also exhibited irregular rhythmic structure, and its development did not follow the consistent trajectories observed in WT vocalizations. These results demonstrate that the Foxp2 gene is critical for normal vocal behavior in juvenile and adult mice, and that Foxp2 mutant mice may provide a tractable model system for the study of the gene's role in general vocal motor control. PMID:26980647

  17. Bex1 knock out mice show altered skeletal muscle regeneration

    SciTech Connect

    Koo, Jae Hyung Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

    2007-11-16

    Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca{sup 2+}/CaM may be involved in skeletal muscle regeneration.

  18. The Majority of Resorptions in Old Mice Are Euploid

    PubMed Central

    Tao, Yong; Liu, X. Johné

    2015-01-01

    Chromosomal abnormality is a leading cause of aging-related infertility, spontaneous abortion and congenital birth defects in humans. Karyotype analyses of spontaneously aborted human fetuses reveal high proportions (~50%) being chromosomal abnormal with the majority being trisomies of various chromosomes. As a model organism, mice are widely used for studies of reproduction and reproductive aging. Like older women, older mice exhibit high incidences of early embryo death. However, it is not known if aneuploidy is prevalent amongst resorptions in older mice. We have karyotyped 65 retarded/resorbed fetuses in 10-month-old C57BL/6 mice, and found that 55 (84.6%±8.8%, with 95% confidence) were euploid. Similarly, of 40 such fetuses from 17 month-old C57BL/6 mice, we found 38 (95±7%, with 95% confidence 95%) being euploid. Therefore, aneuploidy is not a leading cause of embryo death in older mice. PMID:26636341

  19. Energy intake, oxidative stress and antioxidant in mice during lactation

    PubMed Central

    ZHENG, Guo-Xiao; LIN, Jiang-Tao; ZHENG, Wei-Hong; CAO, Jing; ZHAO, Zhi-Jun

    2015-01-01

    Reproduction is the highest energy demand period for small mammals, during which both energy intake and expenditure are increased to cope with elevated energy requirements of offspring growth and somatic protection. Oxidative stress life history theory proposed that reactive oxygen species (ROS) were produced in direct proportion to metabolic rate, resulting in oxidative stress and damage to macromolecules. In the present study, several markers of oxidative stress and antioxidants activities were examined in brain, liver, kidneys, skeletal muscle and small intestine in non-lactating (Non-Lac) and lactating (Lac) KM mice. Uncoupling protein (ucps) gene expression was examined in brain, liver and muscle. During peak lactation, gross energy intake was 254% higher in Lac mice than in Non-Lac mice. Levels of H2O2 of Lac mice were 17.7% higher in brain (P<0.05), but 21.1% (P<0.01) and 14.5% (P<0.05) lower in liver and small intestine than that of Non-Lac mice. Malonadialdehyde (MDA) levels of Lac mice were significantly higher in brain, but lower in liver, kidneys, muscle and small intestine than that of Non-Lac mice. Activity of glutathione peroxidase (GSH-PX) was significantly decreased in brain and liver in the Lac group compared with that in the Non-Lac group. Total antioxidant capacity (T-AOC) activity of Lac mice was significantly higher in muscle, but lower in kidneys than Non-Lac mice. Ucp4 and ucp5 gene expression of brain was 394% and 577% higher in Lac mice than in Non-Lac mice. These findings suggest that KM mice show tissue-dependent changes in both oxidative stress and antioxidants. Activities of antioxidants may be regulated physiologically in response to the elevated ROS production in several tissues during peak lactation. Regulations of brain ucp4 and ucp5 gene expression may be involved in the prevention of oxidative damage to the tissue. PMID:25855228

  20. Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia

    PubMed Central

    D'Ortona, Samantha; Ahnger-Pier, Kathryn; Duan, Biyan; Surana, Neeraj K.; Lu, Roger; Cywes-Bentley, Colette; Gadjeva, Mihaela; Shan, Qiang; Priebe, Gregory P.; Pier, Gerald B.

    2015-01-01

    Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22+ TCRβ+ cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection. PMID:26216419

  1. Diet Induced Obese Mice Are Leptin Insufficient After Weight Reduction

    PubMed Central

    Shi, Haifei; Akunuru, Shailaja; Bierman, John C.; Hodge, Karen M.; Mitchell, M. Chrissy; Foster, Michelle T.; Seeley, Randy J.; Reizes, Ofer

    2016-01-01

    Behavioral therapies aimed at reducing excess body fat result in limited fat loss after dieting. To understand the causes for maintenance of adiposity, high-fat (HF) diet-induced obese (DIO) mice were switched to a low-fat chow diet, and the effects of chow on histological and molecular alterations of adipose tissue and metabolic parameters were examined. DIO mice reduced and stabilized their body weights after being switched to chow (HF-chow), but retained a greater amount of adiposity than chow-fed mice. Reduction in adipocyte volume, not number, caused the decrease in fat mass. HF-chow mice showed normalized circulating insulin and leptin levels, improved glucose tolerance, and reduced inflammatory status in white adipose tissue (WAT). Circulating leptin levels corrected for fat mass were lower in HF-chow mice. Leptin administration was used to test whether reduced leptin level of HF-chow mice inhibited further fat loss. Leptin treatment led to an additional reduction in adiposity. Finally, HF-HF mice had lower mRNA levels of β3- adrenergic receptor (β3-AR) in epididymal WAT compared to chow-fed mice, and diet change led to an increase in the WAT β3-AR mRNA levels that were similar to the levels of chow-fed mice, suggesting an elevation in sympathetic activation of WAT during diet-switch relative to HF-HF mice leading to the reduced leptin level and pro-inflammatory cytokine content. In summary, HF-chow mice were resistant to further fat loss due to leptin insufficiency. Diet alteration from HF to low-fat improved metabolic state of DIO mice, although their adiposity was defended at a higher level. PMID:19373220

  2. Methylphenidate restores novel object recognition in DARPP-32 knockout mice.

    PubMed

    Heyser, Charles J; McNaughton, Caitlyn H; Vishnevetsky, Donna; Fienberg, Allen A

    2013-09-15

    Previously, we have shown that Dopamine- and cAMP-regulated phosphoprotein of 32kDa (DARPP-32) knockout mice required significantly more trials to reach criterion than wild-type mice in an operant reversal-learning task. The present study was conducted to examine adult male and female DARPP-32 knockout mice and wild-type controls in a novel object recognition test. Wild-type and knockout mice exhibited comparable behavior during the initial exploration trials. As expected, wild-type mice exhibited preferential exploration of the novel object during the substitution test, demonstrating recognition memory. In contrast, knockout mice did not show preferential exploration of the novel object, instead exhibiting an increase in exploration of all objects during the test trial. Given that the removal of DARPP-32 is an intracellular manipulation, it seemed possible to pharmacologically restore some cellular activity and behavior by stimulating dopamine receptors. Therefore, a second experiment was conducted examining the effect of methylphenidate. The results show that methylphenidate increased horizontal activity in both wild-type and knockout mice, though this increase was blunted in knockout mice. Pretreatment with methylphenidate significantly impaired novel object recognition in wild-type mice. In contrast, pretreatment with methylphenidate restored the behavior of DARPP-32 knockout mice to that observed in wild-type mice given saline. These results provide additional evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory. These results also indicate that the behavioral deficits in DARPP-32 knockout mice may be restored by the administration of methylphenidate. PMID:23906769

  3. GATA4 Deficiency Impairs Ovarian Function in Adult Mice1

    PubMed Central

    Kyrönlahti, Antti; Vetter, Melanie; Euler, Rosemarie; Bielinska, Malgorzata; Jay, Patrick Y.; Anttonen, Mikko; Heikinheimo, Markku; Wilson, David B.

    2011-01-01

    Transcription factor GATA4 is expressed in granulosa cells and, to a lesser extent, in other ovarian cell types. Studies of mutant mice have shown that interactions between GATA4 and its cofactor, ZFPM2 (also termed FOG2), are required for proper development of the fetal ovary. The role of GATA4 in postnatal ovarian function, however, has remained unclear, in part because of prenatal lethality of homozygous mutations in the Gata4 gene in mice. To circumvent this limitation, we studied ovarian function in two genetically engineered mouse lines: C57BL/6 (B6) female mice heterozygous for a Gata4-null allele, and 129;B6 female mice in which Gata4 is deleted specifically in proliferating granulosa cells using the Cre-loxP recombination system and Amhr2-cre. Female B6 Gata4+/− mice had delayed puberty but normal estrous cycle lengths and litter size. Compared to wild-type mice, the ovaries of gonadotropin-stimulated B6 Gata4+/− mice were significantly smaller, released fewer oocytes, produced less estrogen, and expressed less mRNA for the putative GATA4 target genes Star, Cyp11a1, and Cyp19. Gata4 conditional knockout (cKO) mice had a more severe phenotype, including impaired fertility and cystic ovarian changes. Like Gata4+/− mice, the ovaries of gonadotropin-stimulated cKO mice released fewer oocytes and expressed less Cyp19 than those of control mice. Our findings, coupled with those of other investigators, support the premise that GATA4 is a key transcriptional regulator of ovarian somatic cell function in both fetal and adult mice. PMID:21248289

  4. Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia.

    PubMed

    Gauguet, Stefanie; D'Ortona, Samantha; Ahnger-Pier, Kathryn; Duan, Biyan; Surana, Neeraj K; Lu, Roger; Cywes-Bentley, Colette; Gadjeva, Mihaela; Shan, Qiang; Priebe, Gregory P; Pier, Gerald B

    2015-10-01

    Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22(+) TCR?(+) cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection. PMID:26216419

  5. Overexpression of agouti protein and stress responsiveness in mice.

    PubMed

    Harris, R B; Zhou, J; Shi, M; Redmann, S; Mynatt, R L; Ryan, D H

    2001-07-01

    Ectopic overexpression of agouti protein, an endogenous antagonist of melanocortin receptors' linked to the beta-actin promoter (BAPa) in mice, produces a phenotype of yellow coat color, Type II diabetes, obesity and increased somatic growth. Spontaneous overexpression of agouti increases stress-induced weight loss. In these experiments, other aspects of stress responsiveness were tested in 12-week-old male wild-type mice and BAPa mice. Two hours of restraint on three consecutive days produced greater increases in corticosterone and post-stress weight loss in BAPa than wild-type mice. In Experiment 2, anxiety-type behavior was measured immediately after 12 min of restraint. This mild stress did not produce many changes indicative of anxiety, but BAPa mice spent more time in the dark side of a light-dark box and less time in the open arms of an elevated plus maze than restrained wild-type mice. In a defensive withdrawal test, grooming was increased by restraint in all mice, but the duration of each event was substantially shorter in BAPa mice, possibly due to direct antagonism of the MC4-R by agouti protein. Thus, BAPa mice showed exaggerated endocrine and energetic responses to restraint stress with small differences in anxiety-type behavior compared with wild-type mice. These results are consistent with observations in other transgenic mice in which the melanocortin system is disrupted, but contrast with reports that acute blockade of central melanocortin receptors inhibits stress-induced hypophagia. Thus, the increased stress responsiveness in BAPa mice may be a developmental compensation for chronic inhibition of melanocortin receptors. PMID:11495665

  6. Diacylglycerol Lipase α Knockout Mice Demonstrate Metabolic and Behavioral Phenotypes Similar to Those of Cannabinoid Receptor 1 Knockout Mice

    PubMed Central

    Powell, David R.; Gay, Jason P.; Wilganowski, Nathaniel; Doree, Deon; Savelieva, Katerina V.; Lanthorn, Thomas H.; Read, Robert; Vogel, Peter; Hansen, Gwenn M.; Brommage, Robert; Ding, Zhi-Ming; Desai, Urvi; Zambrowicz, Brian

    2015-01-01

    After creating >4,650 knockouts (KOs) of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1) KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase α or β (Dagla or Daglb), which catalyze biosynthesis of the endocannabinoid (EC) 2-arachidonoylglycerol (2-AG), or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild-type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 47 and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. By contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight (BW) similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride, and total cholesterol levels, and after glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: (1) the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; (2) in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and (3) small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower BW and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric side-effects. PMID:26082754

  7. Vocal Ontogeny in Neotropical Singing Mice (Scotinomys)

    PubMed Central

    Campbell, Polly; Pasch, Bret; Warren, Ashley L.; Phelps, Steven M.

    2014-01-01

    Isolation calls produced by dependent young are a fundamental form of communication. For species in which vocal signals remain important to adult communication, the function and social context of vocal behavior changes dramatically with the onset of sexual maturity. The ontogenetic relationship between these distinct forms of acoustic communication is surprisingly under-studied. We conducted a detailed analysis of vocal development in sister species of Neotropical singing mice, Scotinomys teguina and S. xerampelinus. Adult singing mice are remarkable for their advertisement songs, rapidly articulated trills used in long-distance communication; the vocal behavior of pups was previously undescribed. We recorded 30 S. teguina and 15 S. xerampelinus pups daily, from birth to weaning; 23 S. teguina and 11 S. xerampelinus were recorded until sexual maturity. Like other rodent species with poikilothermic young, singing mice were highly vocal during the first weeks of life and stopped vocalizing before weaning. Production of first advertisement songs coincided with the onset of sexual maturity after a silent period of ≧2 weeks. Species differences in vocal behavior emerged early in ontogeny and notes that comprise adult song were produced from birth. However, the organization and relative abundance of distinct note types was very different between pups and adults. Notably, the structure, note repetition rate, and intra-individual repeatability of pup vocalizations did not become more adult-like with age; the highly stereotyped structure of adult song appeared de novo in the first songs of young adults. We conclude that, while the basic elements of adult song are available from birth, distinct selection pressures during maternal dependency, dispersal, and territorial establishment favor major shifts in the structure and prevalence of acoustic signals. This study provides insight into how an evolutionarily conserved form of acoustic signaling provides the raw material for adult vocalizations that are highly species specific. PMID:25469986

  8. Paeoniflorin attenuates allergic inflammation in asthmatic mice.

    PubMed

    Sun, Jing; Wu, Jinfeng; Xu, Changqing; Luo, Qingli; Li, Bei; Dong, Jingcheng

    2015-01-01

    Paeoniflorin (PF), one of the major active ingredients of Chinese peony, has demonstrated anti-inflammatory and immunoregulatory effects. However, it has remained unclear whether PF treatment can inhibit allergic inflammation in asthma. In this study, we evaluated the effects of PF on pulmonary function and airway inflammation in asthmatic mice. The allergic asthma models were established in BALB/c mice. The mice were sensitized and challenged with ovalbumin. Airway hyperresponsiveness was detected by direct airway resistance analysis. Lung tissues were examined for inflammatory cell infiltration. IL-5, IL-13, IL-17, and eotaxin in bronchoalveolar lavage fluid (BALF) and their mRNA expression in lung tissue were examined by ELISA and realtime PCR, respectively. The total IgE level in serum was measured by ELISA. The protein expression of p-ERK and p-JNK was detected by western blot. Our data showed that PF oral administration significantly reduced airway hyperresponsiveness to aerosolized methacholine and decreased IL-5, IL-13, IL-17 and eotaxin levels in the BALF, and decreased IgE level in the serum. Histological studies showed that PF administration markedly decreased inflammatory infiltration. Similarly, treatment with PF significantly inhibited IL-5, IL-13, IL-17 and eotaxin mRNA expression in lung tissues. The protein expression levels of p-ERK and p-JNK were substantially decreased after oral administration of PF. In summary, PF displayed anti-inflammatory effects in the OVA-induced asthmatic model by decreasing the expression of IL-5, IL-13, IL-17 and eotaxin. These effects were mediated at least partially by inhibiting the activation of MAPK pathway. PMID:25433342

  9. Assessing Cervical Dislocation as a Humane Euthanasia Method in Mice

    PubMed Central

    Carbone, Larry; Carbone, Elizabeth T; Yi, Elizabeth M; Bauer, Diana B; Lindstrom, Krista A; Parker, John M; Austin, Jamie A; Seo, Youngho; Gandhi, Anisha D; Wilkerson, James D

    2012-01-01

    Research investigators often choose to euthanize mice by cervical dislocation (CD) when other methods would interfere with the aims of a research project. Others choose CD to assure death in mice treated with injected or inhaled euthanasia agents. CD was first approved for mouse euthanasia in 1972 by the AVMA Panel on Euthanasia, although scientific assessment of its humaneness has been sparse. Here we compared 4 methods of spinal dislocation–3 targeting the cervical area (CD) and one the thoracic region–in regard to time to respiratory arrest in anesthetized mice. Of the 81 mice that underwent CD by 1 of the 3 methods tested, 17 (21%) continued to breathe, and euthanasia was scored as unsuccessful. Postmortem radiography revealed cervical spinal lesions in 5 of the 17 cases of unsuccessful CD euthanasia. In addition, 63 of the 64 successfully euthanized mice had radiographically visible lesions in the high cervical or atlantooccipital region. In addition, 50 of 64 (78%) mice euthanized successfully had radiographically visible thoracic or lumbar lesions or both. Intentionally creating a midthoracic dislocation in anesthetized mice failed to induce respiratory arrest and death in any of the 18 mice subjected to that procedure. We conclude that CD of mice holds the potential for unsuccessful euthanasia, that anesthesia could be valuable for CD skills training and assessment, and that postmortem radiography has minimal promise in quality-control assessments. PMID:22776194

  10. Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice

    PubMed Central

    Vikramadithyan, Reeba K.; Hu, Yunying; Noh, Hye-Lim; Liang, Chien-Ping; Hallam, Kellie; Tall, Alan R.; Ramasamy, Ravichandran; Goldberg, Ira J.

    2005-01-01

    Direct evidence that hyperglycemia, rather than concomitant increases in known risk factors, induces atherosclerosis is lacking. Most diabetic mice do not exhibit a higher degree of atherosclerosis unless the development of diabetes is associated with more severe hyperlipidemia. We hypothesized that normal mice were deficient in a gene that accelerated atherosclerosis with diabetes. The gene encoding aldose reductase (AR), an enzyme that mediates the generation of toxic products from glucose, is expressed at low levels in murine compared with human tissues. Mice in which diabetes was induced through streptozotocin (STZ) treatment, but not nondiabetic mice, expressing human AR (hAR) crossed with LDL receptor–deficient (Ldlr–/–) C57BL/6 male mice had increased aortic atherosclerosis. Diabetic hAR-expressing heterozygous LDL receptor–knockout mice (Ldlr+/–) fed a cholesterol/cholic acid–containing diet also had increased aortic lesion size. Lesion area at the aortic root was increased by STZ treatment alone but was further increased by hAR expression. Macrophages from hAR-transgenic mice expressed more scavenger receptors and had greater accumulation of modified lipoproteins than macrophages from nontransgenic mice. Expression of genes that regulate regeneration of glutathione was reduced in the hAR-expressing aortas. Thus, hAR increases atherosclerosis in diabetic mice. Inhibitors of AR or other enzymes that mediate glucose toxicity could be useful in the treatment of diabetic atherosclerosis. PMID:16127462

  11. Partial return yoke for MICE step IV and final step

    SciTech Connect

    Witte, H.; Plate, S.; Berg, J. S.; Tarrant, J.; Bross, A.

    2015-05-03

    This paper reports on the progress of the design and construction of a retro-fitted return yoke for the international Muon Ionization Cooling Experiment (MICE). MICE is a proof-of-principle experiment aiming to demonstrate ionization cooling experimentally. In earlier studies we outlined how a partial return yoke can be used to mitigate stray magnetic field in the experimental hall; we report on the progress of the construction of the partial return yoke for MICE Step IV. We also discuss an extension of the Partial Return Yoke for the final step of MICE; we show simulation results of the expected performance.

  12. Fibroblast growth factor 15 deficiency impairs liver regeneration in mice

    PubMed Central

    Kong, Bo; Huang, Jiansheng; Zhu, Yan; Li, Guodong; Williams, Jessica; Shen, Steven; Aleksunes, Lauren M.; Richardson, Jason R.; Apte, Udayan; Rudnick, David A.

    2014-01-01

    Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an endocrine FGF highly expressed in the small intestine of mice. Emerging evidence suggests that FGF15 is critical for regulating hepatic functions; however, the role of FGF15 in liver regeneration is unclear. This study assessed whether liver regeneration is altered in FGF15 knockout (KO) mice following 2/3 partial hepatectomy (PHx). The results showed that FGF15 KO mice had marked mortality, with the survival rate influenced by genetic background. Compared with wild-type mice, the KO mice displayed extensive liver necrosis and marked elevation of serum bile acids and bilirubin. Furthermore, hepatocyte proliferation was reduced in the KO mice because of impaired cell cycle progression. After PHx, the KO mice had weaker activation of signaling pathways that are important for liver regeneration, including signal transducer and activator of transcription 3, nuclear factor-κB, and mitogen-activated protein kinase. Examination of the KO mice at early time points after PHx revealed a reduced and/or delayed induction of immediate-early response genes, including growth-control transcription factors that are critical for liver regeneration. In conclusion, the results suggest that FGF15 deficiency severely impairs liver regeneration in mice after PHx. The underlying mechanism is likely the result of disrupted bile acid homeostasis and impaired priming of hepatocyte proliferation. PMID:24699334

  13. Colonization and pathogenesis of Cryptococcus neoformans in gnotobiotic mice.

    PubMed Central

    Salkowski, C A; Bartizal, K F; Balish, M J; Balish, E

    1987-01-01

    Congenitally immunodeficient nude (nu/nu) mice and their immunocompetent littermates (nu/+) were used to determine whether the absence of thymus-matured T cells would alter the capacity of Cryptococcus neoformans to colonize their mucosal surfaces or enhance their susceptibility to systemic cryptococcosis, or both, following oral challenge. We present data demonstrating that an encapsulated strain of C. neoformans serotype A colonized the alimentary tracts of germfree, conventional, and antibiotic-treated conventional nu/nu mice. Scanning electron microscopy showed that C. neoformans adhered to the epithelial surfaces of the oral cavities, esophagi, and gastrointestinal tracts of monoassociated nu/nu and nu/+ mice, and culture data showed that there were more viable C. neoformans cells in the alimentary tracts of nu/nu mice than of nu/+ mice. Tetracycline-treated conventional nu/nu, but not nu/+, mice were also colonized with C. neoformans following intragastric challenge. C. neoformans-monoassociated and tetracycline-treated conventional nu/nu mice succumbed to disseminated cryptococcosis with cerebral involvement 3 to 4 weeks after oral challenge, whereas no mortality was observed for similarily challenged nu/+ mice. These results demonstrate that an encapsulated strain of C. neoformans can colonize mucosal surfaces and cause systemic cryptococcosis in immunodeficient nu/nu mice, suggesting that the alimentary tract can be a portal of entry for C. neoformans in an immunodeficient host. These data also indicate that functional T cells play an important role in resistance to systemic cryptococcosis of endogenous origin. Images PMID:3305359

  14. Spontaneous Mutagenesis Is Enhanced in Apex Heterozygous Mice

    PubMed Central

    Huamani, Jessica; McMahan, C. Alex; Herbert, Damon C.; Reddick, Robert; McCarrey, John R.; MacInnes, Mark I.; Chen, David J.; Walter, Christi A.

    2004-01-01

    Germ line DNA directs the development of the next generation and, as such, is profoundly different from somatic cell DNA. Spermatogenic cells obtained from young adult lacI transgenic mice display a lower spontaneous mutant frequency and greater in vitro base excision repair activity than somatic cells and tissues obtained from the same mice. However, spermatogenic cells from old lacI mice display a 10-fold higher mutant frequency. This increased spontaneous mutant frequency occurs coincidentally with decreased in vitro base excision repair activity for germ cell and testicular extracts that in turn corresponds to a decreased abundance of AP endonuclease. To directly test whether a genetic diminution of AP endonuclease results in increased spontaneous mutant frequencies in spermatogenic cell types, AP endonuclease heterozygous (Apex+/−) knockout mice were crossed with lacI transgenic mice. Spontaneous mutant frequencies were significantly elevated (approximately twofold) for liver and spleen obtained from 3-month-old Apex+/− lacI+ mice compared to frequencies from Apex+/+ lacI+ littermates and were additionally elevated for somatic tissues from 9-month-old mice. Spermatogenic cells from 9-month-old Apex+/− lacI+ mice were significantly elevated twofold compared to levels for 9-month-old Apex+/+ lacI+ control mice. These data indicate that diminution of AP endonuclease has a significant effect on spontaneous mutagenesis in somatic and germ line cells. PMID:15340075

  15. Factors Affecting Formation of Incomplete Vi Antibody in Mice

    PubMed Central

    Gaines, Sidney; Currie, Julius A.; Tully, Joseph G.

    1965-01-01

    Gaines, Sidney (Walter Reed Army Institute of Research, Washington, D.C.), Julius A. Currie, and Joseph G. Tully. Factors affecting formation of incomplete Vi antibody in mice. J. Bacteriol. 90:635–642. 1965.—Single immunizing doses of purified Vi antigen elicited complete and incomplete Vi antibodies in BALB/c mice, but only incomplete antibody in Cinnamon mice. Three of six other mouse strains tested responded like BALB/c mice; the remaining three, like Cinnamon mice. Varying the quantity of antigen injected or the route of administration failed to stimulate the production of detectable complete Vi antibody in Cinnamon mice. Such antibody was evoked in these animals by multiple injections of Vi antigen or by inoculating them with Vi-containing bacilli or Vi-coated erythrocytes. The early protection afforded by serum from Vi-immunized BALB/c mice coincided with the appearance of incomplete Vi antibody, 1 day prior to the advent of complete antibody. Persistence of incomplete as well as complete antibody in the serum of immunized mice was demonstrated for at least 56 days after injection of 10 μg of Vi antigen. Incomplete Vi antibody was shown to have blocking ability, in vitro bactericidal activity, and the capability of protecting mice against intracerebral as well as intraperitoneal challenge with virulent typhoid bacilli. Production of incomplete and complete Vi antibodies was adversely affected by immunization with partially depolymerized Vi antigens. PMID:16562060

  16. Partial Return Yoke for MICE Step IV and Final Step

    SciTech Connect

    Witte, Holger; Plate, Stephen; Berg, J.Scott; Tarrant, Jason; Bross, Alan

    2015-06-01

    This paper reports on the progress of the design and construction of a retro-fitted return yoke for the international Muon Ionization Cooling Experiment (MICE). MICE is a proof-of-principle experiment aiming to demonstrate ionization cooling experimentally. In earlier studies we outlined how a partial return yoke can be used to mitigate stray magnetic field in the experimental hall; we report on the progress of the construction of the partial return yoke for MICE Step IV. We also discuss an extension of the Partial Return Yoke for the final step of MICE; we show simulation results of the expected performance.

  17. Protocols for nuclear transfer in mice.

    PubMed

    Gao, Shaorong

    2006-01-01

    Cloning by nuclear transfer in mammals has revealed the remarkable ability of an oocyte to reprogram transferred cell nuclei and induce them to recapitulate the developmental program. This chapter summarizes the method used since 1998 for mouse cloning, which differs from that for large animal cloning. A Piezo-drill micromanipulator allows direct injection of nuclei into enucleated mice oocytes instead of the electrofusion method used for introducing a nucleus into an enucleated oocyte of a large animal. After activation, reconstructed embryos are allowed to develop to the morulae or blastocyst stage before transfer into surrogate mothers. PMID:16761716

  18. Genetic predisposition to lymphomas in mice.

    PubMed

    Hiai, H

    1996-10-01

    The spontaneous mouse lymphoma is a model of multifactorial genetic disease. It is induced by the endogenous murine leukemia virus (MuLV), whose genome is inherited as a Mendelian dominant trait. Lymphoma development takes place in multiple stages affected by many host genetic and epigenetic factors. An inbred strain SL/Kh with a high incidence of pre-B lymphomas has been established and the genetic predisposition of SL/Kh mice to lymphomas is being studied in the crosses with other inbred strains of mice. In the cross to the NFS/N lacking endogenous MuLV genome, it has been shown that lymphomas are induced by the expression of Emv-11 provirus (Chr. 7), and the types of B-lineage lymphomas are determined by combinations of the host genes, Esl-1 (Chr. 17) and Foc-1 (Chr. 4). Another gene, Tlsm-1 (Chr. 7) that determines the type of lymphomas to be T-lineage, is identified in the cross with AKR/Ms, with a high incidence of T-lymphomas. The role of the thymus in the development of T-lymphomas in the mouse, and the possible relevance of Tlsm-1 in this step, is discussed. The length of the latent period is determined by a gene Lia-1 (Chr. 17). A maternal resistance factor that is a maternal antibody to MuLV transmitted via milk and that epigenetically inhibits MuLV expression in SL/Ni-Eco-, one of subline of SL/NI mice, has been shown. Weak but definitive maternal resistance also operates in SL/Ni-Eco+, a subline lacking the maternal antibody to MuLV. In the latter, there is a recessive resistance gene Nir-1 (Chr. 4). In the cross with MSM/Ms, a wild mice-derived inbred strain, two resistance genes, Msmr-1 (Chr. 17) and Msmr-2 (Chr. 18), have been identified. In SL/Kh, all of these host genetic and epigenetic factors are favorable for lymphoma development. This model offers not only an understanding of the pathogenesis of virus-induced lymphomas but also may provide starting material for the comparative approach to homologous human diseases. PMID:8916139

  19. Microangiography in Living Mice Using Synchrotron Radiation

    NASA Astrophysics Data System (ADS)

    Yuan, Falei; Wang, Yongting; Guan, Yongjing; Lu, Haiyan; Xie, Bohua; Tang, Yaohui; Xie, Honglan; Du, Guohao; Xiao, Tiqiao; Yang, Guo-Yuan

    2010-07-01

    Traditionally, there are no methods available to detect the fine morphologic changes of cerebrovasculature in small living animals such as rats and mice. Newly developed synchrotron radiation microangiography can achieve a fine resolution of several micrometers and had provided us with a powerful tool to study the cerebral vasculature in small animals. The purpose of this study is to identify the morphology of cerebrovasculature especially the structure of Lenticulostriate arteries (LSAs) in living mice using the synchrotron radiation source at Shanghai Synchrotron Radiation Facility (SSRF) in Shanghai, China. Adult CD-1 mice weighing 35-40 grams were anesthetized. Nonionic iodine (Omnipaque, 350 mg I /mL) was used as a contrast agent. The study was performed at the BL13W1 beam line at SSRF. The beam line was derived from a storage ring of electrons with an accelerated energy of 3.5 GeV and an average beam current of 200 mA. X-ray energy of 33.3 keV was used to produce the highest contrast image. Images were acquired every 172 ms by a x-ray camera (Photonic-Science VHR 1.38) with a resolution of 13 μm/pixel. The optimal dose of contrast agent is 100 μl per injection and the injecting rate is 33 μl/sec. The best position for imaging is to have the mouse lay on its right or left side, with ventral side facing the X-ray source. We observed the lenticulostriate artery for the first time in living mice. Our result show that there are 4 to 5 lenticulostriate branches originating from the root of middle cerebral artery in each hemisphere. LSAs have an average diameter of 43±6.8 μm. There were no differences between LSAs from the left and right hemisphere (p<0.05). These results suggest that synchrotron radiation may provide a unique tool for experimental stroke research.

  20. Methylarginines in Mice with Experimental Atherosclerosis.

    PubMed

    Gilinsky, M A; Sukhovershin, R A; Cherkanova, M S

    2015-11-01

    We studied the dynamics of indexes for the system of endogenous regulation of NO bioavailability. The content of NO synthase inhibitors (monomethylarginine and asymmetric dimethylarginine) in the blood of mice was measured after intraperitoneal injections of a nonionic surfactant poloxamer 407 for 2 and 14 weeks. The concentrations of both methylarginines in animals with atherosclerosis due to 14-week administration of poloxamer were much higher than in control specimens. The amount of arginine and symmetric dimethylarginine practically did not differ from the control. Poloxamer-induced model of atherosclerosis is characterized by increased content of NO synthase inhibitors. These changes contribute to the development of endothelial dysfunction and atherosclerosis. PMID:26601840

  1. Transfer of gut microbiota from lean and obese mice to antibiotic-treated mice

    PubMed Central

    Ellekilde, Merete; Selfjord, Ellika; Larsen, Christian S.; Jakesevic, Maja; Rune, Ida; Tranberg, Britt; Vogensen, Finn K.; Nielsen, Dennis S.; Bahl, Martin I.; Licht, Tine R.; Hansen, Axel K.; Hansen, Camilla H. F.

    2014-01-01

    Transferring gut microbiota from one individual to another may enable researchers to “humanize” the gut of animal models and transfer phenotypes between species. To date, most studies of gut microbiota transfer are performed in germ-free mice. In the studies presented, it was tested whether an antibiotic treatment approach could be used instead. C57BL/6 mice were treated with ampicillin prior to inoculation at weaning or eight weeks of age with gut microbiota from lean or obese donors. The gut microbiota and clinical parameters of the recipients was characterized one and six weeks after inoculation. The results demonstrate, that the donor gut microbiota was introduced, established, and changed the gut microbiota of the recipients. Six weeks after inoculation, the differences persisted, however alteration of the gut microbiota occurred with time within the groups. The clinical parameters of the donor phenotype were partly transmissible from obese to lean mice, in particularly β cell hyperactivity in the obese recipients. Thus, a successful inoculation of gut microbiota was not age dependent in order for the microbes to colonize, and transferring different microbial compositions to conventional antibiotic-treated mice was possible at least for a time period during which the microbiota may permanently modulate important host functions. PMID:25082483

  2. Transfer of gut microbiota from lean and obese mice to antibiotic-treated mice.

    PubMed

    Ellekilde, Merete; Selfjord, Ellika; Larsen, Christian S; Jakesevic, Maja; Rune, Ida; Tranberg, Britt; Vogensen, Finn K; Nielsen, Dennis S; Bahl, Martin I; Licht, Tine R; Hansen, Axel K; Hansen, Camilla H F

    2014-01-01

    Transferring gut microbiota from one individual to another may enable researchers to "humanize" the gut of animal models and transfer phenotypes between species. To date, most studies of gut microbiota transfer are performed in germ-free mice. In the studies presented, it was tested whether an antibiotic treatment approach could be used instead. C57BL/6 mice were treated with ampicillin prior to inoculation at weaning or eight weeks of age with gut microbiota from lean or obese donors. The gut microbiota and clinical parameters of the recipients was characterized one and six weeks after inoculation. The results demonstrate, that the donor gut microbiota was introduced, established, and changed the gut microbiota of the recipients. Six weeks after inoculation, the differences persisted, however alteration of the gut microbiota occurred with time within the groups. The clinical parameters of the donor phenotype were partly transmissible from obese to lean mice, in particularly β cell hyperactivity in the obese recipients. Thus, a successful inoculation of gut microbiota was not age dependent in order for the microbes to colonize, and transferring different microbial compositions to conventional antibiotic-treated mice was possible at least for a time period during which the microbiota may permanently modulate important host functions. PMID:25082483

  3. Comparative toxicity of acephate in laboratory mice, white-footed mice, and meadow voles

    USGS Publications Warehouse

    Rattner, B.A.; Hoffman, D.J.

    1984-01-01

    The LD50 (95% confidence limits) of the organophosphorus insecticide acephate was estimated to be 351, 380, and 321 mg/kg (295?416, 280?516, and 266?388 mg/kg) for CD-1 laboratory mice (Mus musculus), white-footed mice (Peromyscus leucopus noveboracensis), and meadow voles (Microtus pennsylvanicus), respectively. In a second study, these species were provided mash containing 0, 25, 100, and 400 ppm acephate for five days. Brain and plasma cholinesterase activities were reduced in a dose-dependent manner to a similar extent in the three species (inhibition of brain acetyl-cholinesterase averaged for each species ranged from 13 to 22% at 25 ppm, 33 to 42% at 100 ppm, and 56 to 57% at 400 ppm). Mash intake, body or liver weight, plasma enzyme activities (alkaline phosphatase, alanine and aspartate aminotransferase), hepatic enzyme activities (aniline hydroxylase, 7-ethoxycoumarin O-deethylase, and glutathione S-transferase), and cytochrome content (P-450 and b5) were not affected by acephate ingestion, although values differed among species. In a third experiment, mice and voles received 400 ppm acephate for 5 days followed by untreated food for up to 2 weeks. Mean inhibition of brain acetylcholin-esterase for the three species ranged from 47 to 58% on day 5, but by days 12 and 19, activity had recovered to 66 to 76% and 81 to 88% of concurrent control values. These findings indicate that CD-1 laboratory mice, white-footed mice, and meadow voles are equally sensitive to acephate when maintained under uniform laboratory conditions. Several factors (e.g., behavior, food preference, habitat) could affect routes and degree of exposure in the field, thereby rendering some species of wild rodents ecologically more vulnerable to organophosphorus insecticides.

  4. Comparative toxicity of acephate in laboratory mice, white-footed mice and meadow voles

    USGS Publications Warehouse

    Rattner, B.A.; Hoffman, D.J.

    1983-01-01

    The LD50 (95% confidence limits) of the organophosphorus insecticide acephate was estimated to be 351, 380, and 321 mg/kg (295?416, 280?516, and 266?388 mg/kg) for CD-1 laboratory mice (Mus musculus), white-footed mice (Peromyscus leucopus noveboracensis), and meadow voles (Microtus pennsylvanicus), respectively. In a second study, these species were provided mash containing 0, 25, 100, and 400 ppm acephate for five days. Brain and plasma cholinesterase activities were reduced in a dose-dependent manner to a similar extent in the three species (inhibition of brain acetyl-cholinesterase averaged for each species ranged from 13 to 22% at 25 ppm, 33 to 42% at 100 ppm, and 56 to 57% at 400 ppm). Mash intake, body or liver weight, plasma enzyme activities (alkaline phosphatase, alanine and aspartate aminotransferase), hepatic enzyme activities (aniline hydroxylase, 7-ethoxycoumarin O-deethylase, and glutathione S-transferase), and cytochrome content (P-450 and b5) were not affected by acephate ingestion, although values differed among species. In a third experiment, mice and voles received 400 ppm acephate for 5 days followed by untreated food for up to 2 weeks. Mean inhibition of brain acetylcholin-esterase for the three species ranged from 47 to 58% on day 5, but by days 12 and 19, activity had recovered to 66 to 76% and 81 to 88% of concurrent control values. These findings indicate that CD-1 laboratory mice, white-footed mice, and meadow voles are equally sensitive to acephate when maintained under uniform laboratory conditions. Several factors (e.g., behavior, food preference, habitat) could affect routes and degree of exposure in the field, thereby rendering some species of wild rodents ecologically more vulnerable to organophosphorus insecticides.

  5. Silibinin attenuates allergic airway inflammation in mice

    SciTech Connect

    Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  6. Photoperiod and reproduction in female deer mice

    SciTech Connect

    Whitsett, J.M.; Miller, L.L.

    1982-03-01

    Female deer mice were exposed to a short day photoperiod beginning during 1 of 3 stages of life. In the first experiment, exposure to SD during adulthood resulted in a minimal disruption of reproductive condition; many females bore 2 litters after the onset of this treatment. In the second experiment, females reared on SD from weaning matured normally, as measured by vaginal introitus; however, vaginal closure occurred in approximately one-half of these females by 9 weeks of age. In the third experiment, females were born of mothers housed on either an SD or a long day photoperiod, and were continued on the maternal photoperiod until 6 weeks of postnatal age. The SD photoperiod markedly inhibited reproductive maturation as measured by vaginal patency, ovarian weight, and uterine weight. A comparison of reproductive organ weights and vaginal condition provided evidence for the validity of the latter measure as an index of reproductive state. As assayed by the present testing procedure, the sensitivity of the reproductive system to photoperiod decreases as a function of age in female deer mice.

  7. Anti Transglutaminase Antibodies Cause Ataxia in Mice

    PubMed Central

    Boscolo, Sabrina; Lorenzon, Andrea; Sblattero, Daniele; Florian, Fiorella; Stebel, Marco; Marzari, Roberto; Not, Tarcisio; Aeschlimann, Daniel; Ventura, Alessandro; Hadjivassiliou, Marios; Tongiorgi, Enrico

    2010-01-01

    Background Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one. Methods We analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice. Conclusion The serum from CD patients contains anti-TG2, TG3 and TG6 antibodies that may potentially cause ataxia. PMID:20300628

  8. Safety study of Ciprofloxacin in newborn mice.

    PubMed

    Bourgeois, Thomas; Delezoide, Anne-Lise; Zhao, Wei; Guimiot, Fabien; Adle-Biassette, Homa; Durand, Estelle; Ringot, Maud; Gallego, Jorge; Storme, Thomas; Le Guellec, Chantal; Kassaï, Behrouz; Turner, Mark A; Jacqz-Aigrain, Evelyne; Matrot, Boris

    2016-02-01

    Ciprofloxacin, a broad-spectrum antimicrobial agent belonging to the fluoroquinolone family, is prescribed off-label in infants less than one year of age. Ciprofloxacin is included in the European Medicines Agency priority list of off-patent medicinal products requiring evaluation in neonates. This evaluation is undergoing within the TINN (Treat Infections in Neonates) FP7 EU project. As part of the TINN project, the present preclinical study was designed to assess the potential adverse effects of Ciprofloxacin on neurodevelopment, liver and joints in mice. Newborn mice received subcutaneous Ciprofloxacin at 10, 30 and 100 mg/kg/day from 2 to 12 postnatal days. Peak plasma levels of Ciprofloxacin were in the range of levels measured in human neonates. We examined vital functions in vivo, including cardiorespiratory parameters and temperature, psychomotor development, exploratory behavior, arthro-, nephro- and hepato-toxic effects. We found no effect of Ciprofloxacin at 10 and 30 mg/kg/day. In contrast, administration at 100 mg/kg/day delayed weight gain, impaired cardiorespiratory and psychomotor development, caused inflammatory infiltrates in the connective tissues surrounding the knee joint, and moderately increased extramedullary hematopoiesis. The present study pleads for careful watching of cardiorespiratory and motor development in neonates treated with Ciprofloxacin, in addition to the standard surveillance of arthrotoxicity. PMID:26627140

  9. Humanized hemato-lymphoid system mice

    PubMed Central

    Theocharides, Alexandre P.A.; Rongvaux, Anthony; Fritsch, Kristin; Flavell, Richard A.; Manz, Markus G.

    2016-01-01

    Over the last decades, incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system, have been developed and now represent an important research tool in the field. The most significant contributions made by means of humanized mice are the identification of normal and leukemic hematopoietic stem cells, the characterization of the human hematopoietic hierarchy, and their use as preclinical therapy models for malignant hematopoietic disorders. Successful xenotransplantation depends on three major factors: tolerance by the mouse host, correct spatial location, and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules. Each of these can be modified. Experimental approaches include the genetic modification of mice to faithfully express human support factors as non-cross-reactive cytokines, to create free niche space, the co-transplantation of human mesenchymal stem cells, the implantation of humanized ossicles or other stroma, and the implantation of human thymic tissue. Besides the source of hematopoietic cells, the conditioning regimen and the route of transplantation also significantly affect human hematopoietic development in vivo. We review here the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment. PMID:26721800

  10. Characterization of natural fluorescence in mice

    NASA Astrophysics Data System (ADS)

    Djeziri, Salim; Ma, Guobin; Mincu, Niculae; Benyamin Seeyar, Anader; Khayat, Mario

    2008-02-01

    One important challenge for in-vivo imaging fluorescence in cancer research and related pharmaceutical studies is to discriminate the exogenous fluorescence signal of the specific tagged agents from the natural fluorescence. For mice, natural fluorescence is composed of endogenous fluorescence from organs like the skin, the bladder, etc. and from ingested food. The discrimination between the two kinds of fluorescence makes easy monitoring the targeted tissues. Generally, the amplitude of the fluorescence signal depends on the location and on the amount of injected fluorophore, which is limited in in-vivo experiments. This paper exposes some results of natural fluorescence analysis from in-vivo mice experiments using a time domain small animal fluorescence imaging system: eXplore Optix TM. Fluorescence signals are expressed by a Time Point Spread Function (TPSF) at each scan point. The study uses measures of similarity applied purposely to the TPSF to evaluate the discrepancy and/or the homogeneity of scanned regions of a mouse. These measures allow a classification scheme to be performed on the TPSF's based on their temporal shapes. The work ends by showing how the exogenous fluorescence can be distinguished from natural fluorescence by using the TPSF temporal shape.

  11. Scurfy mice: A model for autoimmune disease

    SciTech Connect

    Godfrey, V.L.

    1993-01-01

    Autoimmune disease-the condition in which the body attacks its own tissue-has been an object of public concern recently. Former President George Bush and his wife Barbara both are afflicted with Graves' disease in which the body's own immune system attakcs the thyroid gland. The safety of breast implants was called into question because of evidence that some recipients had developed autoimmune disorders such a rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Women, the media pointed out, have a higher-than-average incidence of many autoimmune disorders. These events suggest the need to know more about what makes the immune system work so well and what makes it go awry. At ORNL's Biology Division, progress is being in understanding the underlying causes of immune disease by studying mice having a disease that causes them to be underdeveloped; to have scaly skin, small ears, and large spleens; to open their eyes late; and to die early. These [open quotes]scurfy[close quotes]mice are helping us better understand the role of the thymus gland in autoimmune disease.

  12. Piperine prevents cholesterol gallstones formation in mice.

    PubMed

    Song, Xiu-Yun; Xu, Shuang; Hu, Jin-Feng; Tang, Jia; Chu, Shi-Feng; Liu, Hang; Han, Ning; Li, Jing-Wei; Zhang, Dong-Ming; Li, Yue-Ting; Chen, Nai-Hong

    2015-03-15

    Biliary cholesterol may contribute to the formation of cholesterol gallstones, and regulation of these levels could be a useful therapeutic strategy for gallstones disease. Piperine (PA) is a potential cholesterol lowering agent. In this study, we assessed the effect and mechanism of PA in preventing cholesterol gallstones formation induced by feeding lithogenic diet containing high cholesterol levels to mice. C57BL/6 inbred mice were fed lithogenic or chow diets for 10 weeks, with or without PA (15, 30 and 60 mg/kg) or ursodeoxycholic acid (UDCA, 60 mg/kg) administration. Cholesterol, phospholipids and crystals in bile, the lipid in serum, pathological changes and proteins expression in liver were analyzed. The results showed that PA could decrease the cholesterol potency and crystals in bile, reduce total cholesterol (TC), triglycerides (TG) and increase high-density lipoprotein/low-density lipoprotein (HDL/LDL) levels in serum. Furthermore, PA treatment reduced liver lipid peroxidation and protected hepatobiliary cells from liver injury by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD). In addition, PA inhibited the expression of ATP-binding cassette transporters G5/8 (ABCG5/8) and liver X receptor (LXR) in liver, and reduced cholesterol transport from the hepatocytes to the gallbladder. It may be the mechanism of PA in preventing cholesterol gallstones formation. PA as a potential drug for prevention cholesterol gallstones merits further investigation. PMID:25645812

  13. Behavioral characterization of P311 knockout mice

    PubMed Central

    Taylor, Gregory A.; Rodriguiz, Ramona M.; Greene, Robert I.; Daniell, Xiaoju; Henry, Stanley C.; Crooks, Kristy R.; Kotloski, Robert; Tessarollo, Lino; Phillips, Lindsey E.; Wetsel, William C.

    2013-01-01

    P311 is an 8-kDa protein that is expressed in many brain regions, particularly the hippocampus, cerebellum and olfactory lobes, and is under stringent regulation by developmental, mitogenic and other physiological stimuli. P311 is thought to be involved in the transformation and motility of neural cells; however, its role in normal brain physiology is undefined. To address this point, P311-deficient mice were developed through gene targeting and their behaviors were characterized. Mutants displayed no overt abnormalities, bred normally and had normal survival rates. Additionally, no deficiencies were noted in motor co-ordination, balance, hearing or olfactory discrimination. Nevertheless, P311-deficient mice showed altered behavioral responses in learning and memory. These included impaired responses in social transmission of food preference, Morris water maze and contextual fear conditioning. Additionally, mutants displayed altered emotional responses as indicated by decreased freezing in contextual and cued fear conditioning and reduced fear-potentiated startle. Together, these data establish P311 as playing an important role in learning and memory processes and emotional responses. PMID:18616608

  14. Humanized hemato-lymphoid system mice.

    PubMed

    Theocharides, Alexandre P A; Rongvaux, Anthony; Fritsch, Kristin; Flavell, Richard A; Manz, Markus G

    2016-01-01

    Over the last decades, incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system, have been developed and now represent an important research tool in the field. The most significant contributions made by means of humanized mice are the identification of normal and leukemic hematopoietic stem cells, the characterization of the human hematopoietic hierarchy, and their use as preclinical therapy models for malignant hematopoietic disorders. Successful xenotransplantation depends on three major factors: tolerance by the mouse host, correct spatial location, and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules. Each of these can be modified. Experimental approaches include the genetic modification of mice to faithfully express human support factors as non-cross-reactive cytokines, to create free niche space, the co-transplantation of human mesenchymal stem cells, the implantation of humanized ossicles or other stroma, and the implantation of human thymic tissue. Besides the source of hematopoietic cells, the conditioning regimen and the route of transplantation also significantly affect human hematopoietic development in vivo. We review here the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment. PMID:26721800

  15. Teratogenic Effects of Pregabalin in Mice

    PubMed Central

    Etemad, Leila; Mohammad, Afshar; Mohammadpour, Amir Hooshang; Vahdati Mashhadi, Nasser; Moallem, Seyed Adel

    2013-01-01

    Objective(s): Anti-epileptic drugs (AEDs) have the potential to affect fetal development throughout pregnancy. Considering the broad therapeutic indications of pregabalin (PGB), its potential teratogenic effects and the levels of homocysteine have been studied. Materials and Methods: Timed-pregnant mice received one of three doses of PGB (20, 40 or 80 mg/kg/day) or the vehicle control during organogenesis, intraperitoneally. The litters were stained and examined for malformations. Total homocysteine (tHcy) was measured in serum from the pregnant mice on GD18. Results: The rate of fetus malformations increased significantly in all treated groups as compared to the control group. The abnormalities included limb, vertebral column and craniofacial abnormalities. The most common abnormality was limb deformity. The percentage of fetal resorption significantly increased at higher doses. There was no significant difference in tHcy concentrations between the treated and control groups. Conclusion: Pregabalin may have potential teratogenic effects even in lower doses, however with less intensity than other AEDs. Therefore, it is suggested that great caution should be taken when prescribing it in pregnancy and further investigation for possible mechaninsms. PMID:24379963

  16. Deletion of ultraconserved elements yields viable mice

    SciTech Connect

    Ahituv, Nadav; Zhu, Yiwen; Visel, Axel; Holt, Amy; Afzal, Veena; Pennacchio, Len A.; Rubin, Edward M.

    2007-07-15

    Ultraconserved elements have been suggested to retainextended perfect sequence identity between the human, mouse, and ratgenomes due to essential functional properties. To investigate thenecessities of these elements in vivo, we removed four non-codingultraconserved elements (ranging in length from 222 to 731 base pairs)from the mouse genome. To maximize the likelihood of observing aphenotype, we chose to delete elements that function as enhancers in amouse transgenic assay and that are near genes that exhibit markedphenotypes both when completely inactivated in the mouse as well as whentheir expression is altered due to other genomic modifications.Remarkably, all four resulting lines of mice lacking these ultraconservedelements were viable and fertile, and failed to reveal any criticalabnormalities when assayed for a variety of phenotypes including growth,longevity, pathology and metabolism. In addition more targeted screens,informed by the abnormalities observed in mice where genes in proximityto the investigated elements had been altered, also failed to revealnotable abnormalities. These results, while not inclusive of all thepossible phenotypic impact of the deleted sequences, indicate thatextreme sequence constraint does not necessarily reflect crucialfunctions required for viability.

  17. Altered myogenesis in Six1-deficient mice.

    PubMed

    Laclef, Christine; Hamard, Ghislaine; Demignon, Josiane; Souil, Evelyne; Houbron, Christophe; Maire, Pascal

    2003-05-01

    Six homeoproteins are expressed in several tissues, including muscle, during vertebrate embryogenesis, suggesting that they may be involved in diverse differentiation processes. To determine the functions of the Six1 gene during myogenesis, we constructed Six1-deficient mice by replacing its first exon with the lacZ gene. Mice lacking Six1 die at birth because of severe rib malformations and show extensive muscle hypoplasia affecting most of the body muscles in particular certain hypaxial muscles. Six1(-/-) embryos have impaired primary myogenesis, characterized, at E13.5, by a severe reduction and disorganisation of primary myofibers in most body muscles. While Myf5, MyoD and myogenin are correctly expressed in the somitic compartment in early Six1(-/-) embryos, by E11.5 MyoD and myogenin gene activation is reduced and delayed in limb buds. However, this is not the consequence of a reduced ability of myogenic precursor cells to migrate into the limb buds or of an abnormal apoptosis of myoblasts lacking Six1. It appears therefore that Six1 plays a specific role in hypaxial muscle differentiation, distinct from those of other hypaxial determinants such as Pax3, cMet, Lbx1 or Mox2. PMID:12668636

  18. Teratogenic effects of noise in mice

    NASA Astrophysics Data System (ADS)

    Murata, M.; Takigawa, H.

    1989-07-01

    This study was undertaken to assess the hazardous effects of noise on embryonic development. The experiment was composed of two parts; one was the observation of the effect due to noise alone, and the other was the observation of the combined effect of noise and known teratogens. ICR mice were exposed to a wide octave-band noise at 100 dB(C) for 6 hours a day in three ways: the first group was exposed to a continuous noise only on day 7 of pregnancy (group "N"), the second was exposed to an intermittent noise (15 min ON/15 min OFF) only on day 7 of pregnancy (group "IN"), and the third was exposed daily to a continuous noise during days 7-12 of pregnancy (group "RN"). Cadmium sulfate or trypan blue was applied as a teratogen, and was administered intraperitoneously on day 7 of pregnancy. On day 18 of pregnancy, mice were sacrificed and the developmental status and external malformations of their fetuses were examined. Each type of noise exposure did not significantly induce embryolethality and fetal growth retardation. However, teratogenicity was observed in groups "N" and "IN". Combined effects of teratogen and noise did not show clear-cut interactions.

  19. Presence of natural autoantibodies in hyperimmunized mice.

    PubMed Central

    Guilbert, B; Mahana, W; Gilbert, M; Mazie, J C; Avrameas, S

    1985-01-01

    Mice were immunized with various antigens in complete Freund's adjuvant following various injection schedules. Hybridomas were produced from the spleens of these immunized mice and examined for production of antibodies directed against the antigen injected and against a panel of self (tubulin, actin, myosin, DNA) and non-self antigens (myoglobin, spectrin, peroxidase, trinitrobenzene). Two to five percent of the hybrids were found to secrete polyspecific antibodies able to react with two or more antigens of the panel. Several of these hybrids were subcloned and expanded into ascites. The monoclonal immunoglobulins they secreted were isolated and shown to be IgM (kappa) and to possess the polyspecific antibody function. Several hybrids were also found to secrete antibodies reacting with the immunizing antigen as well as one or more antigens of the panel. The antibody secreted by one subclone which reacts with both the immunizing antigen, prolactin and one of the panel antigens, TNP, has been isolated using a DNP-immunoadsorbent. The isolated antibody was found to be a monoclonal IgM (kappa) immunoglobulin and to react both with prolactin and TNP. The hypothesis is advanced that cells carrying polyspecific natural antibodies as receptors after a given antigenic stimulation proliferate into cells producing highly specific antibodies for epitopes of that given antigen; the cells with polyspecific receptors will be continuously replaced by new cells probably on bone-marrow origin. Images Figure 1 PMID:3935568

  20. Molecular Hydrogen Attenuates Neuropathic Pain in Mice

    PubMed Central

    Kawaguchi, Masanori; Satoh, Yasushi; Otsubo, Yukiko; Kazama, Tomiei

    2014-01-01

    Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation). When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting. PMID:24941001

  1. Urea Transporter Physiology Studied in Knockout Mice

    PubMed Central

    Li, Xuechen; Chen, Guangping; Yang, Baoxue

    2012-01-01

    In mammals, there are two types of urea transporters; urea transporter (UT)-A and UT-B. The UT-A transporters are mainly expressed in kidney epithelial cells while UT-B demonstrates a broader distribution in kidney, heart, brain, testis, urinary tract, and other tissues. Over the past few years, multiple urea transporter knockout mouse models have been generated enabling us to explore the physiological roles of the different urea transporters. In the kidney, deletion of UT-A1/UT-A3 results in polyuria and a severe urine concentrating defect, indicating that intrarenal recycling of urea plays a crucial role in the overall capacity to concentrate urine. Since UT-B has a wide tissue distribution, multiple phenotypic abnormalities have been found in UT-B null mice, such as defective urine concentration, exacerbated heart blockage with aging, depression-like behavior, and earlier male sexual maturation. This review summarizes the new insights of urea transporter functions in different organs, gleaned from studies of urea transporter knockout mice, and explores some of the potential pharmacological prospects of urea transporters. PMID:22745630

  2. Estrogen sulfotransferase ablation sensitizes mice to sepsis

    PubMed Central

    Chai, Xiaojuan; Guo, Yan; Jiang, Mengxi; Hu, Bingfang; Li, Zhigang; Fan, Jie; Deng, Meihong; Billiar, Timothy R.; Kucera, Heidi; Gaikwad, Nilesh W.; Xu, Meishu; Lu, Peipei; Yan, Jiong; Fu, Haiyan; Liu, Youhua; Yu, Lushan; Huang, Min; Zeng, Su; Xie, Wen

    2015-01-01

    Sepsis is the host's deleterious systemic inflammatory response to microbial infections. Here we report an essential role for the estrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the cecal ligation and puncture (CLP) and lipopolysacharide (LPS) models of sepsis induce the expression of EST and compromise the activity of estrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised estrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes estrogen deactivation and sensitizes mice to CLP-induced inflammatory response. The induction of EST by sepsis is NF-κB dependent and EST is a NF-κB target gene. The reciprocal regulation of inflammation and EST may represent a yet to be explored mechanism of endocrine regulation of inflammation, which has an impact on the clinical outcome of sepsis. PMID:26259151

  3. Staphylococcus-mediated T-cell activation and spontaneous natural killer cell activity in the absence of major histocompatibility complex class II molecules

    NASA Technical Reports Server (NTRS)

    Chapes, S. K.; Hoynowski, S. M.; Woods, K. M.; Armstrong, J. W.; Beharka, A. A.; Iandolo, J. J.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    We used major histocompatibility complex class II antigen-deficient transgenic mice to show that in vitro natural killer cell cytotoxicity and T-cell activation by staphylococcal exotoxins (superantigens) are not dependent upon the presence of major histocompatibility complex class II molecules. T cells can be activated by exotoxins in the presence of exogenously added interleukin 1 or 2 or in the presence of specific antibody without exogenously added cytokines.

  4. Perfluorocarbon emulsion therapy attenuates pneumococcal infection in sickle cell mice.

    PubMed

    Helmi, Nawal; Andrew, Peter W; Pandya, Hitesh C

    2015-05-15

    Impaired immunity and tissue hypoxia-ischemia are strongly linked with Streptococcus pneumoniae pathogenesis in patients with sickle cell anemia. Perfluorocarbon emulsions (PFCEs) have high O2-dissolving capacity and can alleviate tissue hypoxia. Here, we evaluate the effects of intravenous PFCE therapy in transgenic sickle cell (HbSS) mice infected with S. pneumoniae. HbSS and C57BL/6 (control) mice intravenously infected with S. pneumoniae were treated intravenously with PFCE or phosphate-buffered saline (PBS) and then managed in either air/O2 (FiO2 proportion, 50%; hereafter referred to as the PFCE-O2 and PBS-O2 groups) or air only (hereafter, the PFCE-air and PBS-air groups) gas mixtures. Lungs were processed for leukocyte and bacterial counts and cytokine measurements. HbSS mice developed severe pneumococcal infection significantly faster than C57BL/6 mice (Kaplan-Maier analysis, P < .05). PFCE-O2-treated HbSS mice had significantly better survival at 72 hours than HBSS mice treated with PFCE-air, PBS-O2, or PBS-air (P < .05). PFCE-O2-treated HbSS mice also had significantly lower pulmonary leukocyte counts, lower interleukin 1β and interferon γ levels, and higher interleukin 10 levels than PFCE-air-treated HbSS mice. Clearance of S. pneumoniae from lungs of HbSS mice or C57BL/6 mice was not altered by PFCE treatment. Improved survival of PFCE-O₂-treated HbSS mice infected with S. pneumoniae is associated with altered pulmonary inflammation but not enhanced bacterial clearance. PMID:25429101

  5. Aberrant behavioral sensitization by methamphetamine in junctophilin-deficient mice.

    PubMed

    Moriguchi, Shigeki; Nishi, Miyuki; Sasaki, Yuzuru; Takeshima, Hiroshi; Fukunaga, Kohji

    2015-04-01

    Junctophilins (JPs) expressed in the endoplasmic/sarcoplasmic reticulum (ER/SR) interact with the plasma membrane, thereby constructing junctional membrane complexes (JMC). We here reported that double-knockout mice lacking both JP3 and JP4 (JP-DKO mice) exhibit aberrant synaptic plasticity in the corticostriatal circuits and irregular methamphetamine (METH)-induced behavioral sensitization when METH (1.0 mg/kg) was administrated six consecutive days and assessed the striatal glutamatergic population spike (PS) by stimulation of cortical white matter. When we assessed the striatal PS by stimulation of cortical white matter, the long-term depression (LTD) was observed in JP-DKO mouse striatum similar to that in control (JP-double hetero mice (JP-DHE mice)). Importantly, LTD converted to long-term potentiation (LTP) following chronic METH treatment concomitant with behavioral sensitization in JP-DHE mice. LTD in JP-DKO mice, however failed to convert to LTP with lacks of behavioral sensitization. LTP impairment in JP-DKO mice was restored by pretreatment with FK506, calcineurin (CaN) inhibitor, but not with apamin, SK channel inhibitor. In immunoblotting analyses, calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation was significantly increased following METH treatment in the striatum of JP-DHE mice. However, CaMKII autophosphorylation did not changed by METH treatment in the striatum of JP-DKO mouse. The increased CaMKII autophosphorylation was closely associated with elevated CaN activity in JP-DKO mice. The lack of increased CaMKII activity in JP-DKO mice was correlated with the impaired METH-induced behavioral sensitization. Thus, elevated CaN and aberrant CaMKII activities in the striatum of JP-DKO mice likely accounts for lack of METH-induced behavioral sensitization. PMID:24848513

  6. Lumican overexpression exacerbates lipopolysaccharide-induced renal injury in mice.

    PubMed

    Lu, Xiao-Mei; Ma, Ling; Jin, Yu-Nan; Yu, Yan-Qiu

    2015-09-01

    The present study aimed to investigate the role of lumican in mice with endotoxin-induced acute renal failure (ARF). Lumican transgenic mice and wild‑type mice were injected with lipopolysaccharide (LPS; 10 mg/kg) to establish a model of ARF. The mice were sacrificed at 24 h and the blood and renal tissue samples were collected. The value of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured to determine renal function. An ELISA was used to determined the concentrations of renal cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)‑6, IL‑4 and IL‑10. The protein expression levels of Toll-like receptor (TLR4) and nuclear factor (NF)κB in renal tissues were assessed using western blot analysis. Terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling was performed to monitor apoptosis of renal tissue. Light microscopy and electron microscopy were used to observe structural changes in the renal tissues. Following the administration of LPS, the SCr and BUN values of mice in the lumican transgenic group were higher compared with those in the control group. The expression levels of renal TLR4, NFκB, TNFα, IL‑6, IL‑4 and IL‑10 were upregulated in the lumican transgenic mice compared with those in the wild‑type control group. Apoptosis was detected predominantly on the renal tubule. There was a significant difference in the optical density of apoptotic bodies between the control mice and the lumican transgenic mice. Light and electron microscopy demonstrated more severe renal tissue injury in the lumican transgenic mice compared with that in the control mice. In conclusion, LPS may cause excessive apoptosis in the renal tubular cells via the TLR4 signal transduction pathway, a decrease in the number of renal tubular cells and ARF. Lumican may be important in mice with LPS-induced ARF. PMID:26081832

  7. Dysfunctional Muscle and Liver Glycogen Metabolism in mdx Dystrophic Mice

    PubMed Central

    Stapleton, David I.; Lau, Xianzhong; Flores, Marcelo; Trieu, Jennifer; Gehrig, Stefan M.; Chee, Annabel; Naim, Timur; Lynch, Gordon S.; Koopman, René

    2014-01-01

    Background Duchenne muscular dystrophy (DMD) is a severe, genetic muscle wasting disorder characterised by progressive muscle weakness. DMD is caused by mutations in the dystrophin (dmd) gene resulting in very low levels or a complete absence of the dystrophin protein, a key structural element of muscle fibres which is responsible for the proper transmission of force. In the absence of dystrophin, muscle fibres become damaged easily during contraction resulting in their degeneration. DMD patients and mdx mice (an animal model of DMD) exhibit altered metabolic disturbances that cannot be attributed to the loss of dystrophin directly. We tested the hypothesis that glycogen metabolism is defective in mdx dystrophic mice. Results Dystrophic mdx mice had increased skeletal muscle glycogen (79%, (P<0.01)). Skeletal muscle glycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (P<0.0001). Glycogen synthase activity was 12% higher (P<0.05) but glycogen branching enzyme activity was 70% lower (P<0.01) in mdx compared with wild-type mice. The rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 62% lower activity (P<0.01) in mdx mice resulting from a 24% reduction in PKA activity (P<0.01). In mdx mice glycogen debranching enzyme expression was 50% higher (P<0.001) together with starch-binding domain protein 1 (219% higher; P<0.01). In addition, mdx mice were glucose intolerant (P<0.01) and had 30% less liver glycogen (P<0.05) compared with control mice. Subsequent analysis of the enzymes dysregulated in skeletal muscle glycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; P<0.05) as a possible cause of this phenotype. Conclusion We identified that mdx mice were glucose intolerant, and had increased skeletal muscle glycogen but reduced amounts of liver glycogen. PMID:24626262

  8. Decreased Proteasomal Activity Causes Photoreceptor Degeneration in Mice

    PubMed Central

    Ando, Ryo; Noda, Kousuke; Tomaru, Utano; Kamoshita, Mamoru; Ozawa, Yoko; Notomi, Shoji; Hisatomi, Toshio; Noda, Mika; Kanda, Atsuhiro; Ishibashi, Tatsuro; Kasahara, Masanori; Ishida, Susumu

    2014-01-01

    Purpose. To study the retinal degeneration caused by decreased proteasomal activity in β5t transgenic (β5t-Tg) mice, an animal model of senescence acceleration. Methods. β5t-Tg mice and age-matched littermate control (WT) mice were used. Proteasomal activities and protein level of poly-ubiquitinated protein in retinal extracts were quantified. Fundus images of β5t-Tg mice were taken and their features were assessed. For histologic evaluation, the thicknesses of inner nuclear layer (INL), outer nuclear layer (ONL), and photoreceptor outer segment (OS) were measured. For functional analysis, ERG was recorded under scotopic and photopic illumination conditions. Immunofluorescence (IF) staining and TUNEL were performed to investigate the mechanism of photoreceptor degeneration. Results. Chymotrypsin-like activity was partially suppressed in retinal tissues of β5t-Tg mice. Retinal degenerative changes with arterial attenuation were present in β5t-Tg, but not in WT mice. Inner nuclear layer thickness showed no significant change between β5t-Tg and WT mice at 1, 3, 6, and 9 months of age. By contrast, thicknesses of ONL and OS in β5t-Tg mice were significantly decreased at 3, 6, and 9 months compared with those in WT mice. Electroretinograms showed decrease of scotopic a-wave amplitude in β5t-Tg mice. The number of TUNEL-positive cells in ONL were significantly increased in β5t-Tg mice and colocalized with apoptosis-inducing factor, but not with cleaved caspase-3 and -9, indicating that the photoreceptor cell death was induced via a caspase-independent pathway. Conclusions. The current data showed that impaired proteasomal function causes photoreceptor degeneration. PMID:24994871

  9. Decreased hematopoietic progenitor cell mobilization in pearl mice.

    PubMed

    Vallejo, Matthew O; Niemeyer, Glenn P; Vaglenov, Alex; Hock, Tommy; Urie, Bridget; Christopherson, Peter; Lothrop, Clinton D

    2013-10-01

    Neutropenia is common to both Hermansky-Pudlak syndrome type 2 and canine cyclic hematopoiesis (CH) which are caused by mutations in the AP3B1 gene. The purpose of this study was to determine if pearl mice were neutropenic. Complete blood counts (CBCs) and bone marrow differential counts, colony forming unit (CFU) assay, bone marrow lineage negative (lin(-)), Sca(+) and c-kit(+) cells (LSK cells), bone marrow elastase, myeloperoxidase, and cathepsin G enzyme activity were compared in C57Bl6 (Bl/6) and pearl mice. Stress granulopoiesis was evaluated following 200 mg/kg cyclophosphamide or 1 mg/kg bortezomib administration and by limiting dilution bone marrow transplantation. The CBCs and CFUs were determined in Bl/6 and pearl mice following AMD3100 or granulocyte colony-stimulating factor (G-CSF) administration. Pearl mice were not neutropenic and did not have cyclic neutropenia. Bone marrow elastase, myeloperoxidase, and cathepsin G enzyme activity were similar in pearl and Bl/6 mice. The numbers of CFU-G, CFU-GEMM, and LSK cells were increased moderately in pearl mice. Stress granulopoiesis was similar in Bl/6 and pearl mice. CFU assays and CBCs performed on Bl/6 and pearl mice administered AMD3100 resulted in similar results. However, normal mice administered G-CSF had higher peripheral blood neutrophil counts and greater CFU numbers compared with pearl mice. Unlike patients with HPS-2 and dogs with CH, pearl mice did not have neutropenia or CH but had decreased hematopoietic progenitor cell and granulocyte mobilization in response to G-CSF. PMID:23748140

  10. Experimental infection of mice with bovine viral diarrhea virus.

    PubMed

    Seong, Giyong; Oem, Jae-Ku; Lee, Kyung-Hyun; Choi, Kyoung-Seong

    2015-06-01

    The objective of this study was to test the ability of bovine viral diarrhea virus (BVDV) to infect mice. Two mice each were either mock infected or inoculated with one of three BVDV strains by the intraperitoneal (IP) (n = 8) or intranasal (IN) (n = 8) route. All mice were euthanized at day 7 postinfection (p.i.). None of the infected mice exhibited any clinical signs of illness; however, the tissues harvested after BVDV challenge showed significant histopathological changes. Blood samples from five mice that were injected IP and one mouse that was inoculated IN were positive for BVDV by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was used to assess the presence of viral antigen in the organs of mice infected with three BVDV strains. In IP-injected mice, BVDV antigen was detected in the spleen (5/6), mesenteric lymph nodes (4/6), lymphatic tissue of the lung (3/6), lung (1/6), and stomach (1/6) of the infected mice; however, it was not detected in the liver (0/6) or kidney (0/6). In IN-inoculated mice, BVDV antigen was detected in the lung and mesenteric lymph nodes of one BVDV-infected mouse but was not detected in other tissues. The results of this study suggest that the spleen is the most reliable tissue for BVDV antigen detection using IHC in the IP-injected group. Our study demonstrates that mice can be infected by BVDV. This is the first report of BVDV infection in mice. PMID:25850760

  11. Circadian phenotyping of obese and diabetic db/db mice.

    PubMed

    Grosbellet, Edith; Dumont, Stephanie; Schuster-Klein, Carole; Guardiola-Lemaitre, Beatrice; Pevet, Paul; Criscuolo, François; Challet, Etienne

    2016-05-01

    Growing evidence links metabolic disorders to circadian alterations. Genetically obese db/db mice, lacking the long isoform of leptin receptor, are a recognized model of type 2 diabetes. In this study, we aimed at characterizing the potential circadian alterations of db/db mice in comparison to db/+ control mice. By using telemetry devices, we first reported arrhythmicity in general activity of most db/db mice under both light-dark cycle and constant darkness, while their rhythm of body temperature is less dramatically disrupted. Water access restricted to nighttime restores significant rhythmicity in behaviorally arrhythmic db/db mice, indicating a masking effect of polydipsia when water is available ad libitum. Endogenous period of temperature rhythm under constant dark conditions is significantly increased (+30 min) in db/db compared with db/+ mice. Next, we studied the oscillations of clock proteins (PER1, PER2 and BMAL1) in the suprachiasmatic nuclei (SCN), the site of the master clock, and detected no difference according to the genotype. Furthermore, c-FOS and P-ERK1/2 expression in response to a light pulse in late night was significantly increased (+80 and +55%, respectively) in the SCN of these diabetic mice. We previously showed that, in addition to altered activity rhythms, db/db mice exhibit altered feeding rhythm. Therefore, we investigated daily patterns of clock protein expression in medial hypothalamic oscillators involved in feeding behavior (arcuate nucleus, ventro- and dorso-medial hypothalamic nuclei). Compared with db/+ mice, very subtle or no difference in oscillations of PER1 and BMAL1 is found in the medial hypothalamus. Although we did not find a clear link between altered hypothalamic clockwork and behavioral rhythms in db/db mice, our results highlight a lengthened endogenous period and altered photic integration in these genetically obese and diabetic mice. PMID:26144489

  12. Transmission of elk and deer prions to transgenic mice.

    PubMed

    Tamgüney, Gültekin; Giles, Kurt; Bouzamondo-Bernstein, Essia; Bosque, Patrick J; Miller, Michael W; Safar, Jiri; DeArmond, Stephen J; Prusiner, Stanley B

    2006-09-01

    Chronic wasting disease (CWD) is a fatal prion disease in deer and elk. Unique among the prion diseases, it is transmitted among captive and free-ranging animals. To facilitate studies of the biology of CWD prions, we generated five lines of transgenic (Tg) mice expressing prion protein (PrP) from Rocky Mountain elk (Cervus elaphus nelsoni), denoted Tg(ElkPrP), and two lines of Tg mice expressing PrP common to white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus), denoted Tg(DePrP). None of the Tg(ElkPrP) or Tg(DePrP) mice exhibited spontaneous neurologic dysfunction at more than 600 days of age. Brain samples from CWD-positive elk, white-tailed deer, and mule deer produced disease in Tg(ElkPrP) mice between 180 and 200 days after inoculation and in Tg(DePrP) mice between 300 and 400 days. One of eight cervid brain inocula transmitted disease to Tg(MoPrP)4053 mice overexpressing wild-type mouse PrP-A in approximately 540 days. Neuropathologic analysis revealed abundant PrP amyloid plaques in the brains of ill mice. Brain homogenates from symptomatic Tg(ElkPrP) mice produced disease in 120 to 190 days in Tg(ElkPrP) mice. In contrast to the Tg(ElkPrP) and Tg(DePrP) mice, Tg mice overexpressing human, bovine, or ovine PrP did not develop prion disease after inoculation with CWD prions from among nine different isolates after >500 days. These findings suggest that CWD prions from elk, mule deer, and white-tailed deer can be readily transmitted among these three cervid species. PMID:16940522

  13. Surgical Correction of Rectal Prolapse in Laboratory Mice (Mus musculus)

    PubMed Central

    Uchihashi, Mayu; Wilding, Laura A; Nowland, Megan H

    2015-01-01

    Rectal prolapse is a common clinical problem in laboratory mice. This condition may occur spontaneously, develop after genetic manipulations, result from infections with pathogens such as Citrobacter species, or arise secondary to experimental design such as colitis models. The current standard of care at our institution is limited to monitoring mice until tissue becomes ulcerated or necrotic; this strategy often leads to premature euthanasia of valuable animals prior to the study endpoint. Surgical correction of rectal prolapse is performed routinely and with minimal complications in larger species by using manual reduction with placement of a pursestring suture. In this report, we investigated whether the use of a pursestring suture was an effective treatment for mice with rectal prolapse. The procedure includes anesthetizing mice with isoflurane, manually reducing prolapsed tissue, and placing a pursestring suture of 4-0 polydioxanone. We have performed this procedure successfully in 12 mice. Complications included self-trauma, fecal impaction due to lack of defecation, and mutilation of the surgical site by cage mates. Singly housing mice for 7 d postoperatively, applying multimodal analgesia, and releasing the pursestring when indicated eliminated these complications. The surgical repair of rectal prolapses in mice is a minimally invasive procedure that resolves the clinical symptoms of affected animals and reduces the number of mice that are euthanized prematurely prior to the study endpoint. PMID:26442289

  14. Spontaneous alternation and exploration in weaver mutant mice.

    PubMed

    Lalonde, R; Manseau, M; Botez, M I

    1988-12-01

    Weaver mutant mice engaged less in motor activity and hole poking. Weaver mice alternated spontaneously in a 4-trial but not a 2-trial test. These results are similar to those of a previous study with staggerer mutants, in that both are less active. However, weaver mutants are less affected in the spontaneous alternation measure. PMID:3202943

  15. Social Dominance in Male Vasopressin 1b Receptor Knockout Mice

    PubMed Central

    Caldwell, Heather K.; Dike, Obianuju E.; Stevenson, Erica L.; Storck, Kathryn; Young, W. Scott

    2010-01-01

    We have previously reported that mice with a targeted disruption of their vasopressin 1b receptor gene, Avpr1b, have mild impairments in social recognition and reduced aggression. The reductions in aggression are limited to social forms of aggression, i.e., maternal and inter-male aggression, while predatory aggression remains unaffected. To further clarify the role of the Avpr1b in the regulation of social behavior we first examined anxiety-like and depression-like behaviors in Avpr1b knockout (Avpr1b −/−) mice. We then went on to test the ability of Avpr1b −/− mice to form dominance hierarchies. No major differences were found between Avpr1b −/− and wildtype mice in anxiety-like behaviors, as measured using an elevated plus maze and an open field test, or depression-like behaviors, as measured using a forced swim test. In the social dominance study we found that Avpr1b −/− mice are able to form dominance hierarchies, though in early hierarchy formation dominant Avpr1b −/− mice display significantly more mounting behavior on Day 1 of testing compared to wildtype controls. Further, non-socially dominant Avpr1b −/− mice spend less time engaged in attack behavior than wildtype controls. These findings suggest that while Avpr1b −/− mice may be able to form dominance hierarchies they may employ alternate strategies. PMID:20298692

  16. `Mice In Space': evaluation of a new housing system

    NASA Astrophysics Data System (ADS)

    Silva, Mitchell; Liu, Yi; Serradj, Nadjet; Salanova, Michele; Touma, Chadi; Poursaberi, Ahmad; Jamon, Marc; Blottner, Dieter; Cancedda, Ranieri; Giuliani, Alessandra; Rustichelli, Franco; Aerts, Jean-Marie; Vico, Lawrence; D'Hooge, Rudi; Falcetti, Giancarlo; Berckmans, Daniel

    In this project a cage design is being proposed in which mice can be housed in a microgravity environment. The objective of this paper is to describe and evaluate the proposed cage design, by investigating the micro-environment within such a MIS cage, and to quantify the difference in activity between single and double housed mice by using integrated cameras in the top covers of the cages and quantifying the differences in stress levels by fecal hormone extraction. By assessing the gradients in air circulation in the cage, it can be visualized that high air flow gradients exist within the MIS cage. Measuring the 3D temperature distribution showed small temperature gradients, being maximum 0.1 C. Single housed MIS mice showed significant different body weight compared to double housed MIS mice and controls (p¡0.05). The effect of individual or double housing on activity was quantified with images recorded during 25 day trials. There was a significantly difference observed as single housed show significant more activity compared to double housed mice (p¡0.05). No significant difference was found in stress levels between MIS housed mice and control mice. The technical description in this paper should allow researchers to be informed about the possibilities that will come available to do mice experimentations in space. Keywords: mouse, spaceflight, animal housing, cage design, micro environment

  17. Inhalation of two putative Gulf War toxins by mice.

    PubMed

    Repine, John E; Wilson, Paul; Elkins, Nancy; Klawitter, Jelena; Christians, Uwe; Peters, Ben; Smith, Dwight M

    2016-06-01

    We employed our inhalation methodology to examine whether biomarkers of inflammation and oxidative stress would be produced in mice following inhalation of aerosols containing carbonaceous particles or the vapor of pesticides prevalent during the first Gulf War. Exposure to two putative Gulf War Illness toxins, fine airborne particles and the pesticide malathion, increased biomarkers of inflammation and oxidative stress in Friend virus B (FVB) female mice. Mice inhaling particles 24 h before had increased lung lavage and plasma Leukotriene B4 (LTB4) (a biomarker of inflammation) and PGF2α (a biomarker of oxidative stress) levels, lung lavage protein and lung lavage lactic dehydrogenase (LDH) levels. These changes were a function of particle density and exposure time. Compared to particle inhalation, mice inhaling malathion 24 h before had small increase in plasma LTB4 and PGF2α levels but no increase in lung lavage LTB4, lung lavage protein, lung lavage LDH, and lung lavage alveolar macrophage (AM) levels compared to unexposed control mice. AM from particle-exposed mice contained phagocytosed particles, while AM from malathion-exposed mice showed no abnormalities. Our results indicate that inhaling particles or malathion can alter inflammatory and oxidative biomarkers in mice and raise the possibility that these toxins may have altered inflammation and oxidative stress biomarkers in Gulf War-exposed individuals. PMID:26950528

  18. ASSESSMENT OF IMMUNOTOXIC POTENTIAL OF THE FUNGICIDE DINOCAP IN MICE

    EPA Science Inventory

    The immunotoxic potential of dinocap was evaluated in female C57BL/6J mice following in vivo and in vitro exposure to this fungicide. n in vivo studies, groups of mice were dosed by gavage with technical grade dinocap at dosages ranging from 12.5 to 50 mg/kg/d for seven or twelve...

  19. Human Microbiota-Associated Mice: A Model with Challenges.

    PubMed

    Arrieta, Marie-Claire; Walter, Jens; Finlay, B Brett

    2016-05-11

    Human microbiota-associated (HMA) mice have been used extensively in gut microbiome research. Here we discuss ecological and evolutionary aspects of the mammalian-gut microbiome interrelationship that confound the application of HMA mice, and propose experimental designs that increase the likelihood for obtaining meaningful findings. PMID:27173924

  20. NAPHTHALENE TOXICITY IN CD-1 MICE: GENERAL TOXICOLOGY AND IMMUNOTOXICOLOGY

    EPA Science Inventory

    The purpose of this study was to evaluate the acute and subchronic toxicity, and effects on immune function, of naphthalene (NAP) in random-bred CD-1 mice. The acute oral LD50 of this compound was 533 and 710 mg/kg in male and female mice, respectively. Fourteen- and ninety-day d...

  1. Effects of Clostridium botulinum toxins on infant and adult mice.

    PubMed Central

    Wisdom, C; Midura, T F

    1982-01-01

    Toxic supernatants of many Clostridium botulinum type B isolates from various sources, especially those of isolates obtained from cases of infant botulism, appeared to more toxic in infant mice than in adult mice. The significance of this finding in diagnostic situations is discussed. PMID:7044312

  2. EVALUATION OF VACCINATION AGAINST METHYLLYCACONITINE TOXICITY IN MICE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to determine if larkspur toxins conjugated to protein carriers would promote active immunity in mice. Mice were injected with several larkspur toxin-protein conjugates or adjuvant alone to determine if the resulting immunologic response altered animal susceptibility to...

  3. Bone growth and turnover in progesterone receptor knockout mice.

    SciTech Connect

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jaime C.; Waters, Katrina M.; Lydon, John P.; O'Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-05-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

  4. Oxygen effects on mortality of mice infected with Diplococcus pneumoniae

    NASA Technical Reports Server (NTRS)

    Angrick, E. J.; Somerson, N. L.; Weiss, H. S.

    1974-01-01

    Mice infected by intraperitoneal injection of Diplococcus pneumoniae were held at 1 atm in either hypoxic (12%), hyperoxic (75%), or a normal (21%) oxygen environment. Mortality rates indicated prolongation of survival in hypoxia and shortened survival in hyperoxia. Exposure of mice to the experimental gas mixtures prior to inoculation did not alter the results.

  5. BEHAVIORAL AND AUTONOMIC THERMOREGULATION IN MICE EXPOSED TO MICROWAVE RADIATION

    EPA Science Inventory

    Preferred ambient temperature (T) and breathing rate were measured in free-moving mice exposed to 2,450-MHz microwaves. A waveguide-exposure system was imposed with a longitudinal temperature gradient that permitted mice to select their preferred T. Breathing rate was determined ...

  6. Gastrointestinal microecology of BALB/c nude mice.

    PubMed Central

    Brown, J F; Balish, E

    1978-01-01

    The aerobic, facultative, and anaerobic microorganisms cultivable from the stomachs, ilea, ceca, and colons of BALB/c athymic (nu/nu) mice (normal and wasting), thymus-implanted normal nude mice, and their heterozygous (nu/+) littermates were investigated. Ninety-one species representing 23 genera of bacteria and yeasts were isolated from the 27 mice. The wasting nude mice showed significantly lower numbers of lactobacilli in their stomach microbiota than did mice from the other three groups. The littermate animals appeared unique among the four groups in having corynebacteria as a major constituent of their stomach and ileal flora. The normal nude mice appeared to have a more diverse anaerobic stomach flora than their heterozygous littermates. These minor differences are discussed with respect to possible immunological, physiological, and environmental factors as their cause. Because the gastrointestinal microfloras of the mice from the four groups were not radically divergent from each other, it was concluded that loss of T-cell function does not dramatically alter the makeup of the cultivable gastrointestinal microflora in these mice. PMID:697355

  7. Oncogene-induced liver neoplasia in transgenic mice.

    PubMed

    Sandgren, E P; Quaife, C J; Pinkert, C A; Palmiter, R D; Brinster, R L

    1989-06-01

    Models of hepatocarcinogenesis were generated by directing the expression of SV40 T-antigens, an oncogenic mutant of c-H-ras, or c-myc to the liver of transgenic mice using the albumin enhancer/promoter. The majority of mice carrying the ras transgene (group A) were born with enlarged livers and atypical hepatic architecture, and these all died within several days of birth. The remaining ras transgenic mice (group B) had lower levels of hepatic ras expression, exhibited mild hepatic dysplasia but no liver enlargement, and all ultimately died from development of lung tumors. In contrast, the livers of mice expressing T-antigens were relatively normal at birth, by one month displayed marked dysplasia, and by three to seven months developed multiple nodular adenomas and carcinomas. Myc expression caused mild to severe hepatic dysplasia in young mice, and focal hepatic adenomas in some mice over fifteen months of age. Lines of mice expressing ras (group B), T-antigen, or myc were established and crossed with each other to generate dual transgenic mice expressing oncogene pairs. Each combination resulted in accelerated tumor development, suggesting that these oncoproteins can cooperate with one another during multistep hepatic transformation. PMID:2543942

  8. Psychological stress-induced catecholamines accelerates cutaneous aging in mice.

    PubMed

    Romana-Souza, Bruna; Santos Lima-Cezar, Gracineide; Monte-Alto-Costa, Andréa

    2015-12-01

    Psychological stress may be an important extrinsic factor which influences aging process. However, neither study demonstrated the mechanism by which chronic stress participates in skin aging. Aim of this study was to investigate the effects of chronic psychological stress on mice skin. Mice were daily submitted to rotational stress, for 28 days, until euthanasia. After 28 days, mice were killed and normal skin was analyzed. Macroscopically, dorsum skin of chronically stressed mice presented more wrinkled when compared to that of nonstressed mice. In mice skin, chronic stress increased lipid peroxidation, carbonyl protein content, nitrotyrosine levels, neutrophil infiltration, neutrophil elastase, tissue inhibitor of metalloproteinase-1 and metalloproteinase-8 levels. Nevertheless, chronic stress reduced dermis thickness, collagen type I, fibrilin-1 and elastin protein levels in mice skin. In in vitro assays, murine skin fibroblasts were exposed to elevated epinephrine levels plus inhibitors of reactive oxygen species (ROS) and reactive nitrogen species (RNS), fibroblast activity was evaluated in a short time. In skin fibroblast culture, treatment with inhibitors of ROS and RNS synthesis abolished the increase in carbonyl protein content and lipid peroxide accumulation induced by epinephrine. In conclusion, chronic psychological stress may be an important extrinsic factor, which contributes to skin aging in mice. PMID:26541702

  9. ALTERED METHIONINE METABOLISM IN LONG LIVING AMES DWARF MICE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ames dwarf mice (df/df) are deficient in growth hormone, prolactin, and thyroid-stimulating hormone and live significantly longer than their normal siblings. In the current study, we found that the hormone deficiencies affect methionine metabolism. We previously reported that the dwarf mice exhibit ...

  10. Crybb2 deficiency impairs fertility in female mice.

    PubMed

    Gao, Qian; Sun, Li-Li; Xiang, Fen-Fen; Gao, Li; Jia, Yin; Zhang, Jian-Rong; Tao, Hai-Bo; Zhang, Jun-Jie; Li, Wen-Jie

    2014-10-10

    Beta-B2-crystallin (CRYBB2), encoded by Crybb2 gene, is a major protein in the mammalian eye lens that plays an important role in maintaining the transparency of the ocular lens. However, CRYBB2 also plays important roles in many extra-lenticular tissues and organs such as the retina, brain and testis. Our previous studies demonstrated that male Crybb2 deficient (Crybb2(-/-)) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2(-/-) mice exhibited reduced ovary weights and shorter estrous cycle percentages. Here we specifically investigated the role of CRYBB2 in the female reproductive system. Our studies revealed that ovaries from female Crybb2(-/-) mice exhibited significantly reduced numbers of primordial, secondary and pre-ovulatory follicles when compared with WT mice, while the rate of atretic follicles was also increased. Additionally, fewer eggs were collected from the oviduct of Crybb2(-/-) female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of female Crybb2(-/-) mice, while progesterone levels were lower in diestrus cycles. Furthermore, the expression of survival and cell cycle genes, Bcl-2, Cdk4 and Ccnd2, were significantly decreased in granulosa cells isolated from female Crybb2(-/-) mice, consistent with the predominant expression of CRYBB2 in ovarian granulosa cells. Our results reveal a critical role for CRYBB2 in female fertility and specific effects on the proliferation and survival status of ovarian granulosa cells. PMID:25245288

  11. Delayed stabilization of dendritic spines in fragile X mice

    PubMed Central

    Cruz-Martín, Alberto; Crespo, Michelle; Portera-Cailliau, Carlos

    2010-01-01

    Fragile X syndrome (FXS) causes mental impairment and autism through transcriptional silencing of the Fmr1 gene, resulting in the loss of the RNA-binding protein FMRP. Cortical pyramidal neurons in affected individuals and Fmr1 knockout (KO) mice have an increased density of dendritic spines. The mutant mice also show defects in synaptic and experience-dependent circuit plasticity, which are known to be mediated in part by dendritic spine dynamics. We used in vivo time-lapse imaging with 2-photon microscopy through cranial windows in male and female neonatal mice to test the hypothesis that dynamics of dendritic protrusions are altered in KO mice during early postnatal development. We find that layer 2/3 neurons from wild type mice exhibit a rapid decrease in dendritic spines dynamics during the first two postnatal weeks, as immature filopodia and protospines are replaced by mushroom spines. In contrast, KO mice show a developmental delay in the downregulation of spine turnover and in the transition from immature to mature spine subtypes. Blockade of metabotropic glutamate receptor (mGluR) signaling, which reverses some adult phenotypes of KO mice, accentuated this immature protrusion phenotype in KO mice. Thus, absence of FMRP delays spine stabilization and dysregulated mGluR signaling in FXS may partially normalize this early synaptic defect. PMID:20534828

  12. CD4+ T cells from collagen-induced arthritic mice are essential to transfer arthritis into severe combined immunodeficient mice.

    PubMed Central

    Kadowaki, K M; Matsuno, H; Tsuji, H; Tunru, I

    1994-01-01

    The role of T lymphocytes in the adoptive transfer of collagen-induced arthritis (CIA) in DBA/1J mice to severe combined immunodeficient (SCID) mice was investigated. Spleen cells from non-immunized, type I collagen (CI) or type II collagen (CII)-immunized DBA/1J mice were injected into SCID mice which lack functional T and B cells. Specific antigenic stimulation of arthritogenic cells was required since only lymphocytes from arthritic CIA mice plus simultaneous administration of CII transferred arthritis to 11 of 12 SCID mice with a marked increase in CII antibody titre. However, CI-immunized or non-immunized DBA/1J mice cells did not induce arthritis in SCID mice. SCID recipients of pre-arthritic CIA lymphocytes presented increase in CII antibody, but showed no clinical signs of arthritis, suggesting that antibodies to CII alone can not induce CIA. Depletion of CD4+ T cells inhibited the transfer of arthritis to SCID mice, with a decrease in CII antibody titre in chimaeras. In contrast, depletion of CD8+ T cells enhanced the onset of arthritis in SCID mice. The results imply that CD4+ T cells are required for the induction of CIA. In addition, CD8+ T cells might have a suppressive role in the etiology of this disease. It is probable that memory CD4+ T cells stimulate production of antibodies to CII and subsequent arthritis. This study clarifies the role of T lymphocytes in the transfer of CIA to SCID mice. Images Fig. 1 Fig. 2 PMID:7914155

  13. Developmental toxicity of perfluorononanoic acid in mice.

    PubMed

    Das, Kaberi P; Grey, Brian E; Rosen, Mitchell B; Wood, Carmen R; Tatum-Gibbs, Katoria R; Zehr, R Daniel; Strynar, Mark J; Lindstrom, Andrew B; Lau, Christopher

    2015-01-01

    Perfluorononanoic acid (PFNA) is a ubiquitous and persistent environmental contaminant. Although its levels in the environment and in humans are lower than those of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA), a steady trend of increases in the general population in recent years has drawn considerable interest and concern. Previous studies with PFOS and PFOA have indicated developmental toxicity in laboratory rodent models. The current study extends the evaluation of these adverse outcomes to PFNA in mice. PFNA was given to timed-pregnant CD-1 mice by oral gavage daily on gestational day 1-17 at 1, 3, 5 or 10mg/kg; controls received water vehicle. Dams given 10mg/kg PFNA could not carry their pregnancy successfully and effects of this dose group were not followed. Similar to PFOS and PFOA, PFNA at 5mg/kg or lower doses produced hepatomegaly in the pregnant dams, but did not affect the number of implantations, fetal viability, or fetal weight. Mouse pups were born alive and postnatal survival in the 1 and 3mg/kg PFNA groups was not different from that in controls. In contrast, although most of the pups were also born alive in the 5mg/kg PFNA group, 80% of these neonates died in the first 10 days of life. The pattern of PFNA-induced neonatal death differed somewhat from those elicited by PFOS or PFOA. A majority of the PFNA-exposed pups survived a few days longer after birth than those exposed to PFOS or PFOA, which typically died within the first 2 days of postnatal life. Surviving neonates exposed to PFNA exhibited dose-dependent delays in eye opening and onset of puberty. In addition, increased liver weight seen in PFNA-exposed offspring persisted into adulthood and was likely related to the persistence of the chemical in the tissue. Evaluation of gene expression in fetal and neonatal livers revealed robust activation of peroxisome proliferator-activated receptor-alpha (PPARα) target genes by PFNA that resembled the responses of PFOA. Our results indicate that developmental toxicity of PFNA in mice is comparable to that of PFOS and PFOA, and that these adverse effects are likely common to perfluoroalkyl acids that persist in the body. PMID:25543169

  14. Silver nanoparticles cause complications in pregnant mice

    PubMed Central

    Zhang, Xi-Feng; Park, Jung-Hyun; Choi, Yun-Jung; Kang, Min-Hee; Gurunathan, Sangiliyandi; Kim, Jin-Hoi

    2015-01-01

    Background Silver nanoparticles (AgNPs) have attracted much interest and have been used for antibacterial, antifungal, anticancer, and antiangiogenic applications because of their unique properties. The increased usage of AgNPs leads to a potential hazard to human health. However, the potential effects of AgNPs on animal models are not clear. This study was designed to investigate the potential impact of AgNPs on pregnant mice. Methods The synthesis of AgNPs was performed using culture extracts of Bacillus cereus. The synthesized AgNPs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. AgNPs were administrated into pregnant mice via intravenous infusion at 1.0 mg/kg doses at 6.5 days postcoitum (dpc). At 13.5, 15.5, and 17.5 dpc, the pregnant mice were euthanized, and the embryo and placenta were isolated. The meiotic status of oocytes was evaluated. DNA methylation studies were performed, and aberrant imprinting disrupted fetal, placental, and postnatal development. Quantitative real-time polymerase chain reaction analysis and Western blot were used to analyze various gene expressions. Results The synthesized AgNPs were uniformly distributed and were spherical in shape with an average size of 8 nm. AgNPs exposure increased the meiotic progression of female germ cells in the fetal mouse ovaries, and maternal AgNP exposure significantly disrupted imprinted gene expression in 15.5 dpc embryos and placentas, such as Ascl2, Snrpn, Kcnq1ot1, Peg3, Zac1, H19, Igf2r, and Igf2; DNA methylation studies revealed that AgNPs exposure significantly altered the methylation levels of differentially methylated regions of Zac1. Conclusion The results from this study indicated that early exposure to AgNPs has the potential to disrupt fetal and postnatal health through epigenetic changes in the embryo and abnormal development of the placenta. These results can contribute to research involved in the safe use of various biomedical applications of AgNPs and improves the understanding of the development of AgNPs in biomedical applications. PMID:26622177

  15. Nmur1-/- mice are not protected from cutaneous inflammation.

    PubMed

    Abbondanzo, Susan J; Manfra, Denise J; Chen, Shu-Cheng; Pinzon-Ortiz, Maria; Sun, Yongliang; Phillips, Jonathan E; Laverty, Maureen; Vassileva, Galya; Hu, Weiwen; Yang, Shijun; Gustafson, Eric L; Fine, Jay S; Hedrick, Joseph A

    2009-01-23

    Neuromedin U (Nmu) is a neuropeptide expressed primarily in the gastrointestinal tract and central nervous system. Previous reports have identified two G protein-coupled receptors (designated Nmur1 and Nmur2) that bind Nmu. Recent reports suggest that Nmu mediates immune responses involving mast cells, and Nmur1 has been proposed to mediate these responses. In this study, we generated mice with an Nmur1 deletion and then profiled the responses of these mice in a cutaneous inflammation model utilizing complete Freund's adjuvant (CFA). We report here that mice lacking Nmur1 had normal inflammation responses with moderate changes in serum cytokines compared to Nmur1(+/+) littermates. Although differences in IL-6 were observed in mice lacking Nmu peptide, these mice exhibited a normal response to CFA. Our data argues against a major role for Nmur1 in mediating the reported inflammatory functions of NmU. PMID:19070594

  16. Generation and Characterization of dickkopf3 Mutant Mice

    PubMed Central

    del Barco Barrantes, Ivan; Montero-Pedrazuela, Ana; Guadao-Ferraz, Ana; Obregon, Maria-Jesus; Martinez de Mena, Raquel; Gailus-Durner, Valrie; Fuchs, Helmut; Franz, Tobias J.; Kalaydjiev, Svetoslav; Klempt, Martina; Hlter, Sabine; Rathkolb, Birgit; Reinhard, Claudia; Morreale de Escobar, Gabriella; Bernal, Juan; Busch, Dirk H.; Wurst, Wolfgang; Wolf, Eckhard; Schulz, Holger; Shtrom, Svetlana; Greiner, Erich; Hrab de Angelis, Martin; Westphal, Heiner; Niehrs, Christof

    2006-01-01

    dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, and most clinical chemistry parameters. Since Dkk3 was proposed to function as thyroid hormone binding protein, we have analyzed deiodinase activities, as well as thyroid hormone levels. Mutant mice are euthyroid, and the data do not support a relationship of dkk3 with thyroid hormone metabolism. Altered phenotypes in dkk3 mutant mice were observed in the frequency of NK cells, immunoglobulin M, hemoglobin, and hematocrit levels, as well as lung ventilation. Furthermore, dkk3-deficient mice display hyperactivity. PMID:16508007

  17. Corynebacterium kutscheri and its alleged avirulent variant in mice.

    PubMed Central

    Hirst, R. G.; Olds, R. J.

    1978-01-01

    Corynebacterium kutscheri and its alleged avirulent variant were re-examined in C57Bl/6 and Swiss Lynch mice. It was confirmed that while C57Bl/6 mice were resistant and Swiss Lynch susceptible to C. kutscheri, the alleged atypical variant was avirulent in both mouse strains. However, following immunosuppression of C57Bl/6 mice with hydrocortisone acetate, it was not possible to reactivate latent C. kutscheri or the alleged atypical variant; this was contrary to previous reports. Moreover, sequential hysterectomy derivation over four generations of C57Bl/6 mice did not eliminate their resistance to C. kutscheri compared with conventionally born animals. Vaccination with live attenuated C. kutscheri protected susceptible mice against virulent challenge; vaccination with the alleged atypical variant afforded no such protection. The suggested role of the alleged avirulent variant in resistance to C. kutscheri is challenged and an alternative explanation of such resistance is proposed. PMID:649947

  18. New findings in gene knockout, mutant and transgenic mice.

    PubMed

    Bartke, Andrzej

    2008-01-01

    During the past year, some novel genetic modifications were shown to alter the lifespan of mice, thus expanding the list of genes and physiological processes that influence mammalian aging. Considerable progress was also made in identifying putative mechanisms of extended longevity in previously described gene knockouts, mutants and transgenics. In addition, new leads concerning mechanisms of aging were derived from studies of gene knockout mice in which aging is accelerated. Among the important findings from the period July 2006 to July 2007: Core body temperature was shown to influence longevity in homeothermic animals; a Surf1 gene knockout extended lifespan in mice; separate studies using Little and Snell dwarf mice found stress resistance enhancements correlated with longevity gains; and mice heterozygous for deletion of insulin receptor substrate 2 (IRS-2) lived longer than normal animals, while animals with homozygous or heterozygous deletion of IRS-2 selectively in the brain exhibited comparable extension of lifespan and various symptoms of delayed aging. PMID:18053667

  19. Induction of follistatin precedes gastric transformation in gastrin deficient mice

    SciTech Connect

    Kang Weiqun; Saqui-Salces, Milena; Zavros, Yana; Merchant, Juanita L.

    2008-11-21

    We previously showed that antral gastric tumors develop in gastrin-deficient (Gas{sup -/-}) mice. Therefore Gas{sup -/-}mice were studied sequentially over 12 months to identify molecular mechanisms underlying gastric transformation. Fundic atrophy developed by 9 months in Gas{sup -/-} mice. Antral mucosal hyperplasia developed coincident with the focal loss of TFF1 and Muc5AC. Microarray analysis of 12 month Gas{sup -/-} tumors revealed an increase in follistatin, an activin/BMP antagonist. We found that elevated follistatin expression occurred in the proliferative neck zone of hyperplastic antrums, in antral tumors of Gas{sup -/-} mice, and also in human gastric cancers. Follistatin induced cyclin D1 and the trefoil factors TFF1 and TFF2 in a gastric cancer cell line. We concluded that antral hyperplasia in Gas{sup -/-} mice involves amplification of mucous cell lineages due to follistatin, suggesting its role in the development of antral gastric tumors.

  20. Defective limbic system in mice lacking the tailless gene.

    PubMed

    Monaghan, A P; Bock, D; Gass, P; Schwäger, A; Wolfer, D P; Lipp, H P; Schütz, G

    1997-12-01

    The gene tailless is a member of the superfamily of genes that encode transcription factors of the ligand-activated nuclear receptor type, and is expressed in the invertebrate and vertebrate brain. In mice, its transcripts are restricted to the periventricular zone of the forebrain, the site of origin of neurons and glia. Here we use homologous recombination to generate mice that lack a functional tailless protein. Homozygous mutant mice are viable at birth, indicating that tailless is not required for prenatal survival; however, adult mutant mice show a reduction in the size of rhinencephalic and limbic structures, including the olfactory, infrarhinal and entorhinal cortex, amygdala and dentate gyrus. Both male and female mice are more aggressive than usual and females lack normal maternal instincts. These animals therefore enable a molecular approach to be taken towards understanding the genetic architecture and morphogenesis of the forebrain. PMID:9394001

  1. Cochlear function in mice following inhalation of brevetoxin-3

    PubMed Central

    Benson, Janet M.; Stagner, Barden B.; Martin, Glen K.; Friedman, Melissa; Durr, Sarah E.; Gomez, Andrea; McDonald, Jacob; Fleming, Lora E.; Backer, Lorraine C.; Baden, Daniel G.; Bourdelais, Andrea; Naar, Jerome; Lonsbury-Martin, Brenda L.

    2009-01-01

    Brevetoxin-3 was shown previously to adversely affect central auditory function in goldfish. The present study evaluated the effects of exposure to this agent on cochlear function in mice using the 2f1-f2 distortion-product otoacoustic emission (DPOAE). Towards this end, inbred CBA/CaJ mice were exposed to a relatively high concentration of brevetoxin-3 (∼400 μg/m3) by nose-only inhalation for a 2-h period. Further, a subset of these mice received a second exposure a day later that lasted for an additional 4 h. Mice exposed only once for 2 h did not exhibit any notable cochlear effects. Similarly, mice exposed two times, for a cumulative dose of 6 h, exhibited essentially no change in DPOAE levels. PMID:15902474

  2. [Development of a hepatitis B virus carrier transgenic mice model].

    PubMed

    Caner, Müge; Arat, Sezen; Bircan, Rifat

    2008-01-01

    The studies for the development of transgenic mice models which provide important profits for the studies concerning immunopathogenesis of hepatitis B virus (HBV) infections are in progress since 20 years. For this purpose different lineages bearing whole HBV genome or selected viral genes have been developed and their usage in clarifying the HBV replication and pathogenesis mechanisms have been emphasized. The aim of this study was to develop and breed a HBV carrier mice model. In the study the full HBV genome has been transferred to mouse embryos by microinjection procedure. Following transgenic manipulation, the HBV carriers among the daughter mice have been detected by molecular methods in which HBV-DNA replication and expression have been shown. The manipulations for transgene transfers have been performed in TUBITAK Marmara Research Center Transgene Laboratory, Gebze, Istanbul. The HBV-DNA carrier mice have been demonstrated by polymerase chain reaction (PCR) using the DNA samples obtained from tail tissues and also by dot-blot hybridization of the mice sera. Integrated HBV-DNA has been detected by applying in-situ hybridization to the liver tissue sections. HBV-DNA expression has been shown by reverse transcriptase PCR method with total RNA molecules that have been isolated from the liver tissues of the HBV-DNA carrier mice. HBsAg has been detected in the liver by immunohistochemical method, and HBsAg and HBeAg have additionally been demonstrated by ELISA. HBV genome, expression of the genome and the expression products have been determined in approximately 10% of the mice of which HBV-DNA have been transferred. By inbreeding heterozygote carrier mice, homozygote HBV transgenic mice line have been obtained. These HBV transgenic mice are the first lineages developed in our country. It is hopefully thought that this HBV carrier transgenic mouse model may contribute to the studies on the pathogenesis of HBV infections which are important health problems in the world as well as in Turkey. PMID:18444564

  3. Running Promotes Wakefulness and Increases Cataplexy in Orexin Knockout Mice

    PubMed Central

    España, Rodrigo A.; McCormack, Sarah L.; Mochizuki, Takatoshi; Scammell, Thomas E.

    2007-01-01

    Study Objective: People with narcolepsy and mice lacking orexin/hypocretin have disrupted sleep/wake behavior and reduced physical activity. Our objective was to identify physiologic mechanisms through which orexin deficiency reduces locomotor activity. Design: We examined spontaneous wheel running activity and its relationship to sleep/wake behavior in wild type (WT) and orexin knockout (KO) mice. Additionally, given that physical activity promotes alertness, we also studied whether orexin deficiency reduces the wake-promoting effects of exercise. Measurements and Results: Orexin KO mice ran 42% less than WT mice. Their ability to run appeared normal as they initiated running as often as WT mice and ran at normal speeds. However, their running bouts were considerably shorter, and they often had cataplexy or quick transitions into sleep after running. Wheel running increased the total amount of wakefulness in WT and orexin KO mice similarly, however, KO mice continued to have moderately fragmented sleep/wake behavior. Wheel running also doubled the amount of cataplexy by increasing the probability of transitioning into cataplexy. Conclusions: Orexin KO mice run significantly less than normal, likely due to sleepiness, imminent cataplexy, or a reduced motivation to run. Orexin is not required for the wake-promoting effects of wheel running given that both WT and KO mice had similar increases in wakefulness with running wheels. In addition, the clear increase in cataplexy with wheel running suggests the possibility that positive emotions or reward can trigger murine cataplexy, similar to that seen in people and dogs with narcolepsy. Citation: España RA; McCormack SL; Mochizuki T; Scammell TE. Running promotes wakefulness and increases cataplexy in orexin knockout mice. SLEEP 2007;30(11):1417-1425. PMID:18041476

  4. Acetaminophen-induced acute liver injury in HCV transgenic mice

    SciTech Connect

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  5. Probiotics Protect Mice from Ovariectomy-Induced Cortical Bone Loss

    PubMed Central

    Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H.; Farman, Helen H.; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

    2014-01-01

    The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice. PMID:24637895

  6. Hepatic toxicity of dronedarone in mice: role of mitochondrial ?-oxidation.

    PubMed

    Felser, Andrea; Stoller, Andrea; Morand, Rjane; Schnell, Dominik; Donzelli, Massimiliano; Terracciano, Luigi; Bouitbir, Jamal; Krhenbhl, Stephan

    2014-09-01

    Dronedarone is an amiodarone-like antiarrhythmic drug associated with severe liver injury. Since dronedarone inhibits mitochondrial respiration and ?-oxidation in vitro, mitochondrial toxicity may also explain dronedarone-associated hepatotoxicity in vivo. We therefore studied hepatotoxicity of dronedarone (200mg/kg/day for 2 weeks or 400mg/kg/day for 1 week by intragastric gavage) in heterozygous juvenile visceral steatosis (jvs(+/-)) and wild-type mice. Jvs(+/-) mice have reduced carnitine stores and are sensitive for mitochondrial ?-oxidation inhibitors. Treatment with dronedarone 200mg/kg/day had no effect on body weight, serum transaminases and bilirubin, and hepatic mitochondrial function in both wild-type and jvs(+/-) mice. In contrast, dronedarone 400mg/kg/day was associated with a 10-15% drop in body weight, and a 3-5-fold increase in transaminases and bilirubin in wild-type mice and, more accentuated, in jvs(+/-) mice. In vivo metabolism of intraperitoneal (14)C-palmitate was impaired in wild-type, and, more accentuated, in jvs(+/-) mice treated with 400mg/kg/day dronedarone compared to vehicle-treated mice. Impaired ?-oxidation was also found in isolated mitochondria ex vivo. A likely explanation for these findings was a reduced activity of carnitine palmitoyltransferase 1a in liver mitochondria from dronedarone-treated mice. In contrast, dronedarone did not affect the activity of the respiratory chain ex vivo. We conclude that dronedarone inhibits mitochondrial ?-oxidation in and ex vivo, but not the respiratory chain. Jvs(+/-) mice are slightly more sensitive for the effect of dronedarone on mitochondrial ?-oxidation than wild-type mice. The results suggest that inhibition of mitochondrial ?-oxidation is an important mechanism of hepatotoxicity associated with dronedarone. PMID:24881592

  7. Involvement of microRNA Lethal-7a in the Regulation of Embryo Implantation in Mice

    PubMed Central

    Liu, Wei-Min; Pang, Ronald T. K.; Cheong, Ana W. Y.; Ng, Ernest H. Y.; Lao, Kaiqin; Lee, Kai-Fai; Yeung, William S. B.

    2012-01-01

    MicroRNAs interact with multiple mRNAs resulting in their degradation and/or translational repression. This report used the delayed implantation model to determine the role of miRNAs in blastocysts. Dormant blastocysts in delayed implanting mice were activated by estradiol. Differential expression of 45 out of 238 miRNAs examined was found between the dormant and the activated blastocysts. Five of the nine members of the microRNA lethal-7 (let-7) family were down-regulated after activation. Human blastocysts also had a low expression of let-7 family. Forced-expression of a family member, let-7a in mouse blastocysts decreased the number of implantation sites (let-7a: 1.1±0.4; control: 3.8±0.4) in vivo, and reduced the percentages of blastocyst that attached (let-7a: 42.0±8.3%; control: 79.0±5.1%) and spreaded (let-7a: 33.5±2.9%; control: 67.3±3.8%) on fibronectin in vitro. Integrin-β3, a known implantation-related molecule, was demonstrated to be a target of let-7a by 3′-untranslated region reporter assay in cervical cancer cells HeLa, and Western blotting in mouse blastocysts. The inhibitory effect of forced-expression of let-7a on blastocyst attachment and outgrowth was partially nullified in vitro and in vivo by forced-expression of integrin-β3. This study provides the first direct evidence that let-7a is involved in regulating the implantation process partly via modulation of the expression of integrin-β3. (200 words). PMID:22623977

  8. Copper metabolism in mottled mouse (Mus musculus) mutants. Studies of blotchy (Moblo) mice and a comparison with brindled (Mobr) mice.

    PubMed Central

    Mann, J R; Camakaris, J; Francis, N; Danks, D M

    1981-01-01

    1. Copper concentrations were low in many organs of Moblo/Y mice, but very high in the gut. Absorption of 64Cu was seen to be very low when related to the absorption of cyano[57Co]cobalamin. The results in Moblo/+ mice were intermediate. 2. Copper therapy temporarily ameliorated many effects of the mutation in Moblo/Y mice, but did not improve the rate of weight gain as has been achieved previously in Mobr/Y mice. Lower capacity for a 'depot dose' effect at the site of injection may explain the difference. 3. The distribution of 64Cu after administration into the bloodstream of Moblo/Y mice altered from an initially normal state to one that resembled the abnormal distribution of pre-existing copper by 48 h. This indicated that the later mechanisms of copper distribution were at fault. Moblo/+ mice were equally affected. 4. The alteration of copper homoeostasis in blotchy mice was similar to that observed in brindled mice previously and in the present studies, although generally less severe. This is consistent with allelism of the two mutations. PMID:7197928

  9. Longitudinal Frequencies of Blood Leukocyte Subpopulations Differ between NOD and NOR Mice but Do Not Predict Diabetes in NOD Mice

    PubMed Central

    Telieps, Tanja; Köhler, Meike; Treise, Irina; Foertsch, Katharina; Adler, Thure; Busch, Dirk H.; Hrabě de Angelis, Martin; Verschoor, Admar; Adler, Kerstin; Bonifacio, Ezio; Ziegler, Anette-Gabriele

    2016-01-01

    Immune phenotyping provides insight into disease pathogenesis and prognostic markers. Trajectories from age of 4 to 36 weeks were modeled for insulin autoantibodies and for leukocyte subpopulations in peripheral blood from female NOD (n = 58) and NOR (n = 22) mice. NOD mice had higher trajectories of insulin autoantibodies, CD4+ and CD8+ T lymphocytes, B lymphocytes, IgD+IgM− B lymphocytes, and NK cells and lower trajectories of CD4+CD25+ T lymphocytes, IgM+ B lymphocytes, granulocytes, and monocytes than NOR mice (all p < 0.001). Of these, only the increased IAA trajectory was observed in NOD mice that developed diabetes as compared to NOD mice that remained diabetes-free. Therefore, the profound differences in peripheral blood leukocyte proportions observed between the diabetes-prone NOD mice and the diabetes-resistant mice do not explain the variation in diabetes development within NOD mice and do not provide markers for diabetes prediction in this model. PMID:26966692

  10. Heart Rate and Electrocardiography Monitoring in Mice

    PubMed Central

    Ho, David; Zhao, Xin; Gao, Shumin; Hong, Chull; Vatner, Dorothy E.; Vatner, Stephen F.

    2011-01-01

    The majority of current cardiovascular research involves studies in genetically engineered mouse models. The measurement of heart rate is central to understanding cardiovascular control under normal conditions, with altered autonomic tone, superimposed stress or disease states, both in wild type mice as well as those with altered genes. Electrocardiography (ECG) is the “gold standard” using either hard wire or telemetry transmission. In addition, heart rate is measured or monitored from the frequency of the arterial pressure pulse or cardiac contraction, or by pulse oximetry. For each of these techniques, discussions of materials and methods, as well as advantages and limitations are covered. However, only the direct ECG monitoring will determine not only the precise heart rates but also whether the cardiac rhythm is normal or not. PMID:21743842

  11. Metabolomic profiling of tumor-bearing mice.

    PubMed

    Wettersten, Hiromi I; Ganti, Sheila; Weiss, Robert H

    2014-01-01

    Metabolomics is one of the newcomers among the "omics" techniques, perhaps also constituting the most relevant for the study of pathophysiological conditions. Metabolomics may indeed yield not only disease-specific biomarkers but also profound insights into the etiology and progression of a variety of human disorders. Various metabolomic approaches are currently available to study oncogenesis and tumor progression in vivo, in murine tumor models. Many of these models rely on the xenograft of human cancer cells into immunocompromised mice. Understanding how the metabolism of these cells evolves in vivo is critical to evaluate the actual pertinence of xenograft models to human pathology. Here, we discuss various tumor xenograft models and methods for their metabolomic profiling to provide a short guide to investigators interested in this field of research. PMID:24924138

  12. A microfluidics cytometer for mice anemia detection.

    PubMed

    Ju, Yanrui; Song, Jian; Geng, Zhaoxin; Zhang, Hongze; Wang, Wei; Xie, Lide; Yao, Weijuan; Li, Zhihong

    2012-11-01

    The design and fabrication of a microfluidic cytometer system and its application for reticulocyte detection are described. This chip can count the target cells, which are focused at the detection window without sheath flow. This cytometer system based on optimized epifluoresence has a competitive advantage in the signal-to-noise ratio. Induced fluorescence from the reticulocyte binded with antibody is detected by the optical module and then transformed into the electronic signal by a photo multiplier tube. After signal processing, the results are automatically read out by a digital module and displayed on the system. To evaluate this microfluidic cytometer system, experiments employing polystyrene (PS) micro beads and induced reticulocyte of mice anemia are carried out, respectively, and the results illustrate that the microfluidic cytometer system is effective in detecting the reticulocyte. PMID:22907472

  13. p53 suppresses tetraploid development in mice.

    PubMed

    Horii, Takuro; Yamamoto, Masamichi; Morita, Sumiyo; Kimura, Mika; Nagao, Yasumitsu; Hatada, Izuho

    2015-01-01

    Mammalian tetraploid embryos die in early development because of defects in the epiblast. Experiments with diploid/tetraploid chimeric mice, obtained via the aggregation of embryonic stem cells, clarified that while tetraploid cells are excluded from epiblast derivatives, diploid embryos with tetraploid extraembryonic tissues can develop to term. Today, this method, known as tetraploid complementation, is usually used for rescuing extraembryonic defects or for obtaining completely embryonic stem (ES) cell-derived pups. However, it is still unknown why defects occur in the epiblast during mammalian development. Here, we demonstrated that downregulation of p53, a tumour suppressor protein, rescued tetraploid development in the mammalian epiblast. Tetraploidy in differentiating epiblast cells triggered p53-dependent cell-cycle arrest and apoptosis, suggesting the activation of a tetraploidy checkpoint during early development. Finally, we found that p53 downregulation rescued tetraploid embryos later in gestation. PMID:25752699

  14. Dispersing brush mice prefer habitat like home

    PubMed Central

    Mabry, Karen E; Stamps, Judy A

    2007-01-01

    During natal dispersal, young animals leave their natal area and search for a new area to live. In species in which individuals inhabit different types of habitat, experience with a natal habitat may increase the probability that a disperser will select the same type of habitat post-dispersal (natal habitat preference induction or NHPI). Despite considerable interest in the ecological and the evolutionary implications of NHPI, we lack empirical evidence that it occurs in nature. Here we show that dispersing brush mice (Peromyscus boylii) are more likely to search and settle within their natal habitat type than expected based on habitat availability. These results document the occurrence of NHPI in nature and highlight the relevance of experience-generated habitat preferences for ecological and evolutionary processes. PMID:18077253

  15. Closed-Loop Optogenetic Intervention in Mice

    PubMed Central

    Oijala, Mikko; Soltesz, Ivan

    2014-01-01

    Optogenetic interventions offer novel ways of probing, in a temporally specific manner, the roles of specific cell types in neuronal network functions of awake, behaving animals. Despite the unique potential for temporally specific optogenetic interventions in disease states, a major hurdle in its broad application to unpredictable brain states in a laboratory setting is constructing a real-time responsive system. We recently created a closed-loop system for stopping spontaneous seizures in chronically epileptic mice using optogenetic intervention. This system performs with very high sensitivity and specificity, and the strategy is relevant not only to epilepsy, but can also be used to react in real time, with optogenetic or other interventions, to diverse brain states. The protocol presented here is highly modular and requires variable time to perform. We describe the basic construction of a complete system, and include our downloadable custom closed-loop detection software which can be employed for this purpose. PMID:23845961

  16. Tumor angiogenesis in mice and men.

    PubMed

    Alani, Rhoda M; Silverthorn, Courtney F; Orosz, Kate

    2004-06-01

    Over the past decade much research has focused on understanding the molecular pathways that regulate the development of a tumor-associated vasculature. In 1999, Lyden and colleagues showed that mice deficient in one to three Id1 or Id3 alleles could not support the growth of tumor xenografts due to defects in tumor-associated angiogenesis. Three recently published manuscripts have now re-examined the role of Id genes in the development of a tumor-associated vasculature using more clinically relevant tumor model systems. Remarkably, all three studies have found strikingly different results compared to the original xenograft data published in 1999. Below we review the current understanding of the role of Id genes in the development of a tumor-associated vasculature given the most recent data and suggest ways in which animal tumor model systems might be put to better use to provide more clinically relevant information. PMID:15153806

  17. Investigating mechanisms of myopia in mice

    PubMed Central

    Pardue, Machelle T.; Stone, Richard A.; Iuvone, P. Michael

    2013-01-01

    While genetic and environmental factors have been shown to control visually-guided eye growth and influence myopia development, investigations into the intersection of these two factors in controlling refractive development have been limited by the lack of a genetically modifiable animal model. Technological advances have now made it possible to assess refractive state and ocular biometry in the small mouse eye and therefore to exploit the many genetic mouse mutants to investigate mechanisms of visually-guided eye growth. This review considers the benefits and challenges of studying refractive development in mice, compares the results of refractive error and ocular biometry from wild-type strains and genetic models in normal laboratory visual environments or with disrupted visual input, and discusses some of the remaining challenges in interpreting data from the mouse to validate and standardize methods between labs. PMID:23305908

  18. MICE, the international Muon Ionization Cooling Experiment

    NASA Astrophysics Data System (ADS)

    Heidt, Chris

    2013-04-01

    Ionization Cooling is the only practical solution to preparing high brilliance muon beams for a neutrino factory or muon collider. MICE is under development at the Rutherford Appleton Laboratory (UK). It is characterized by exquisite emittance determination by 6D measurement of individual particles, a cooling section comprising 23 MV of acceleration at 200 MHz and 3 liquid hydrogen absorbers totaling 1m of liquid hydrogen on the path of 140-240 MeV/c muons. Thebeam has already been commissioned successfully and first measurements of beam emittance performed. We are setting up for the final high precision emittance determination and the measurements of cooling in Li Hydrogen. The design offers opportunities to observe cooling with various absorbers and several optics configurations. Results will be compared with detailed simulations of cooling channel performance to ensure full understanding of the cooling process. Progress towards the full cooling experiment with RF re-acceleration will also be reported.

  19. Circadian responses to endotoxin treatment in mice.

    PubMed

    Marpegán, Luciano; Bekinschtein, Tristán A; Costas, Monica A; Golombek, Diego A

    2005-03-01

    We tested the ability of Escherichia coli lipopolysaccharide (LPS) to phase-shift the activity circadian rhythm in C57Bl/6J mice. Intraperitoneal administration of 25 microg/kg LPS induced photic-like phase delays (-43+/-10 min) during the early subjective night. These delays were non-additive to those induced by light at CT 15, and were reduced by the previous administration of sulfasalazine, a NF-kappaB activation inhibitor. At CT 15, LPS induced c-Fos expression in the dorsal area of the suprachiasmatic nuclei (SCN). Our results suggest that the activation of the immune system should be considered an entraining signal for the murine circadian clock. PMID:15710463

  20. Chorioallantoic placenta defects in cloned mice

    SciTech Connect

    Wakisaka-Saito, Noriko; Kohda, Takashi . E-mail: tkhoda.epgn@tmd.ac.jp; Inoue, Kimiko; Ogonuki, Narumi; Miki, Hiromi; Hikichi, Takafusa; Mizutani, Eiji; Wakayama, Teruhiko; Kaneko-Ishino, Tomoko; Ogura, Atsuo; Ishino, Fumitoshi

    2006-10-13

    Somatic cell nuclear transfer technology has been applied to produce live clones successfully in several mammalian species, but the success rates are very low. In mice, about half of the nuclear transfer embryos undergo implantation, but very few survive to term. We undertook detailed histological analyses of placentas from cloned mouse embryos generated from cumulus cells at 10.5 dpc of pregnancy, by which stage most clones have terminated their development. At 10.5 dpc, the extraembryonic tissues displayed several defined histological patterns, each reflecting their stage of developmental arrest. The most notable abnormality was the poor development of the spongiotrophoblast layer of diploid cells. This is in contrast to the placental hyperplasia frequently observed in somatic clones at 12.5 dpc or later stages. A variety of structural abnormalities were also observed in the embryos. Both placental and embryonic defects likely contribute to the low success rate of the mouse clones.

  1. Peripheral toxicity of hemicholinium-3 in mice.

    PubMed Central

    Freeman, J. J.; Kosh, J. W.; Parrish, J. S.

    1982-01-01

    1 The site (i.e. peripheral or central) of the toxicity produced by hemicholinium-3 in mice was investigated. 2 Hemicholinium-3 was measured fluorometrically and acetylcholine was determined by gas chromatography after intraventricular or intraperitoneal administration of hemicholinium-3. 3 Hemicholinium-3 was not detected in the brain nor were acetylcholine levels decreased in the brain after systemic administration. 4 The dose-response curve following intraventricular administration demonstrated that hemicholinium-3 was not as lethal after central administration as it was after peripheral administration. 5 Approximately 24% of a 75 microgram intraventricular dose of hemicholinium-3 was found in the periphery at death. 6 These results suggest that hemicholinium-3 manifests its toxicity primarily in the periphery. PMID:7139185

  2. An isolated tumor perfusion model in mice

    PubMed Central

    Duyverman, Annique M M J; Kohno, Mitsutomo; Roberge, Sylvie; Fukumura, Dai; Duda, Dan G; Jain, Rakesh K

    2012-01-01

    The role of stromal cells in the tumor microenvironment has been extensively characterized. We and others have shown that stromal cells may participate in several steps of the metastatic cascade. This protocol describes an isolated tumor perfusion model that enables studies of cancer and stromal cell shedding. It could also be used to study the effects of therapies interfering with the shedding of tumor cells or fragments, circulating (stem) cells or biomarkers. Primary tumors are grown in a microenvironment in which stromal cells express GFP ubiquitously. Tumors are implanted orthotopically or can be implanted ectopically. As a result, all tumor-associated stromal cells express GFP. This technique can be used to detect and study the role of stromal cells in tumor fragments within the circulation in mice. Studying the role of stromal cells in circulating tumor fragments using this model may take 210 weeks, depending on the growth rate of the primary tumor. PMID:22441293

  3. Striatonigral control of movement velocity in mice.

    PubMed

    Bartholomew, Ryan A; Li, Haofang; Gaidis, Erin J; Stackmann, Michelle; Shoemaker, Charles T; Rossi, Mark A; Yin, Henry H

    2016-04-01

    The basal ganglia have long been implicated in action initiation. Using three-dimensional motion capture, we quantified the effects of optogenetic stimulation of the striatonigral (direct) pathway on movement kinematics. We generated transgenic mice with channelrhodopsin-2 expression in striatal neurons that express the D1-like dopamine receptor. With optic fibres placed in the sensorimotor striatum, an area known to contain movement velocity-related single units, photo-stimulation reliably produced movements that could be precisely quantified with our motion capture programme. A single light pulse was sufficient to elicit movements with short latencies (<30 ms). Increasing stimulation frequency increased movement speed, with a highly linear relationship. These findings support the hypothesis that the sensorimotor striatum is part of a velocity controller that controls rate of change in body configurations. PMID:27091436

  4. Metformin improves healthspan and lifespan in mice

    PubMed Central

    Martin-Montalvo, Alejandro; Mercken, Evi M.; Mitchell, Sarah J.; Palacios, Hector H.; Mote, Patricia L.; Scheibye-Knudsen, Morten; Gomes, Ana P.; Ward, Theresa M.; Minor, Robin K.; Blouin, Marie-José; Schwab, Matthias; Pollak, Michael; Zhang, Yongqing; Yu, Yinbing; Becker, Kevin G.; Bohr, Vilhelm A.; Ingram, Donald K.; Sinclair, David A.; Wolf, Norman S.; Spindler, Stephen R.; Bernier, Michel; de Cabo, Rafael

    2013-01-01

    Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced LDL and cholesterol levels without a decrease in caloric intake. At a molecular level, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation. Our results indicate that these actions may contribute to the beneficial effects of metformin on healthspan and lifespan. These findings are in agreement with current epidemiological data and raise the possibility of metformin-based interventions to promote healthy aging. PMID:23900241

  5. p53 Suppresses Tetraploid Development in Mice

    PubMed Central

    Horii, Takuro; Yamamoto, Masamichi; Morita, Sumiyo; Kimura, Mika; Nagao, Yasumitsu; Hatada, Izuho

    2015-01-01

    Mammalian tetraploid embryos die in early development because of defects in the epiblast. Experiments with diploid/tetraploid chimeric mice, obtained via the aggregation of embryonic stem cells, clarified that while tetraploid cells are excluded from epiblast derivatives, diploid embryos with tetraploid extraembryonic tissues can develop to term. Today, this method, known as tetraploid complementation, is usually used for rescuing extraembryonic defects or for obtaining completely embryonic stem (ES) cell-derived pups. However, it is still unknown why defects occur in the epiblast during mammalian development. Here, we demonstrated that downregulation of p53, a tumour suppressor protein, rescued tetraploid development in the mammalian epiblast. Tetraploidy in differentiating epiblast cells triggered p53-dependent cell-cycle arrest and apoptosis, suggesting the activation of a tetraploidy checkpoint during early development. Finally, we found that p53 downregulation rescued tetraploid embryos later in gestation. PMID:25752699

  6. Quench anaylsis of MICE spectrometer superconducting solenoid

    SciTech Connect

    Kashikhin, Vladimir; Bross, Alan; Prestemon, Soren; / /LBL, Berkeley

    2011-09-01

    MICE superconducting spectrometer solenoids fabrication and tests are in progress now. First tests of the Spectrometer Solenoid discovered some issues which could be related to the chosen passive quench protection system. Both solenoids do not have heaters and quench propagation relied on the 'quench back' effect, cold diodes, and shunt resistors. The solenoids have very large inductances and stored energy which is 100% dissipated in the cold mass during a quench. This makes their protection a challenging task. The paper presents the quench analysis of these solenoids based on 3D FEA solution of coupled transient electromagnetic and thermal problems. The simulations used the Vector Fields QUENCH code. It is shown that in some quench scenarios, the quench propagation is relatively slow and some areas can be overheated. They describe ways of improving the solenoids quench protection in order to reduce the risk of possible failure.

  7. VCSELs for Optical Mice and Sensing

    NASA Astrophysics Data System (ADS)

    Grabherr, Martin; Moench, Holger; Pruijmboom, Armand

    A real mass application for VCSELs is their use in optical mice and sensing. As illumination source for sensing applications VCSELs offer a better performance than LEDs. The even more advanced approach of laser self-mixing interference sensors allows a next step in integration, accuracy and new application fields. This chapter summarizes the major requirements towards VCSELs in illumination for sensing applications and gives typical specifications. A detailed description of the production process and the achieved reproducibility makes clear that these VCSELs are ideally suited for production in large quantities. In the second half of the chapter the self-mixing interference method is described in more detail and a highly integrated two axes laser Doppler interferometer is shown. This product is designed for a laser mouse but offers a number of other sensing applications.

  8. Induction of Interferon in Mice by Mycoplasmas

    PubMed Central

    Rinaldo, Charles R.; Cole, Barry C.; Overall, James C.; Glasgow, Lowell A.

    1974-01-01

    Interferon was induced in mice after intraperitoneal inoculation with four different mycoplasmas. Peak levels of between 100 and 300 U of interferon per ml were attained by 6 h postinfection with each of the mycoplasmas except Mycoplasma arthritidis, which induced higher titers (400 to 11,800 U/ml) by this time. A fifth mycoplasma, M. pulmonis, induced interferon inconsistently and at a later (72 to 96 h) time. Mycoplasmatales virus MVL51 and sterile mycoplasmal broth did not stimulate interferon production in vivo. All of the mycoplasmas and MVL51 failed to induce interferon in murine spleen cell, peritoneal exudate cell, or peripheral blood leukocyte cultures. Preinfecting the mycoplasmas with MVL51 or treating the organisms with trypsin or dilutions of specific antisera did not enhance their ability to induce interferon in vitro. PMID:4373395

  9. Translating Treg Therapy in Humanized Mice

    PubMed Central

    Hahn, Susanne A.; Bellinghausen, Iris; Trinschek, Bettina; Becker, Christian

    2015-01-01

    Regulatory T cells (Treg) control immune cell function as well as non-immunological processes. Their far-reaching regulatory activities suggest their functional manipulation as a means to sustainably and causally intervene with the course of diseases. Preclinical tools and strategies are however needed to further test and develop interventional strategies outside the human body. “Humanized” mouse models consisting of mice engrafted with human immune cells and tissues provide new tools to analyze human Treg ontogeny, immunobiology, and therapy. Here, we summarize the current state of humanized mouse models as a means to study human Treg function at the molecular level and to design strategies to harness these cells for therapeutic purposes. PMID:26697017

  10. Chronopharmacodynamics and Chronopharmacokinetics of Pethidine in Mice

    PubMed Central

    Li, Xiping; Xu, Yanjiao; Liu, Dong

    2014-01-01

    Background Many studies have demonstrated that the pharmacokinetics and pharmacodynamics of analgesic drugs vary according to the circadian time of drug administration. This study aims at determining whether the analgesic effect and pharmacokinetics of pethidine in male BALB/c mice are influenced by administration time. Methods A hot-plate test was used to evaluate the analgesic effect after pethidine (20 mg/kg) or saline injection at different dosing times. Mouse blood samples were collected at different intervals after dosing at 9:00 am and 9:00 pm, and were determined via liquid chromatographytandem mass spectrometry (LCMS/MS). Results A significant 24-h rhythm was observed in the latency to thermal response at 30 min after dosing, with the peak during the dark phase and the nadir during the light phase. Tolerance to analgesic effect was produced after chronic pethidine injection at 9:00 am or 9:00 pm, and the recovery from tolerance was faster during the dark phase. The peak concentration (Cmax) and area under the concentrationtime curve (AUC) of pethidine and its metabolite norpethidine were significantly higher during the dark phase than during the light phase, but the total serum clearance (CL/F) exhibited the opposite trend. The rhythm of drug plasma concentration was positively correlated with the analgesic effect. Conclusion These results suggest that the pharmacodynamics and pharmacokinetics of pethidine in mice vary significantly according to the dosing time, which implies that the time of administration should be considered in the rational clinical use of pethidine to maximise analgesia and minimise the adverse effects. PMID:25025283

  11. Oxytocin decreases sweet taste sensitivity in mice.

    PubMed

    Sinclair, Michael S; Perea-Martinez, Isabel; Abouyared, Marianne; St John, Steven J; Chaudhari, Nirupa

    2015-03-15

    Oxytocin (OXT) suppresses food intake and lack of OXT leads to overconsumption of sucrose. Taste bud cells were recently discovered to express OXT-receptor. In the present study we tested whether administering OXT to wild-type mice affects their licking behavior for tastants in a paradigm designed to be sensitive to taste perception. We injected C57BL/6J mice intraperitoneally (i.p.) with 10mg/kg OXT and assayed their brief-access lick responses, motivated by water deprivation, to NaCl (300mM), citric acid (20mM), quinine (0.3mM), saccharin (10mM), and a mix of MSG and IMP (100mM and 0.5mM respectively). OXT had no effect on licking for NaCl, citric acid, or quinine. A possible effect of OXT on saccharin and MSG+IMP was difficult to interpret due to unexpectedly low lick rates to water (the vehicle for all taste solutions), likely caused by the use of a high OXT dose that suppressed licking and other behaviors. A subsequent experiment focused on another preferred tastant, sucrose, and employed a much lower OXT dose (0.1mg/kg). This modification, based on our measurements of plasma OXT following i.p. injection, permitted us to elevate plasma [OXT] sufficiently to preferentially activate taste bud cells. OXT at this low dose significantly reduced licking responses to 0.3M sucrose, and overall shifted the sucrose concentration - behavioral response curves rightward (mean EC50saline=0.362M vs. EC50OXT=0.466M). Males did not differ from females under any condition in this study. We propose that circulating oxytocin is another factor that modulates taste-based behavior. PMID:25554481

  12. Human immunodeficiency virus encephalitis in SCID mice.

    PubMed Central

    Persidsky, Y.; Limoges, J.; McComb, R.; Bock, P.; Baldwin, T.; Tyor, W.; Patil, A.; Nottet, H. S.; Epstein, L.; Gelbard, H.; Flanagan, E.; Reinhard, J.; Pirruccello, S. J.; Gendelman, H. E.

    1996-01-01

    The human immunodeficiency virus (HIV) is neuroinvasive and commonly causes cognitive and motor deficits during the later stages of viral infection. (referred to as HIV dementia). The mechanism(s) for disease revolves around secretory products produced from immune-activated brain macrophages/microglia. Recently, we developed an animal model system for HIV dementia that contains xenografts of HIV-1-infected cells inoculated into brains of mice with severe combined immunodeficiency (SCID). This animal system was used to quantitatively evaluate HIV-induced neuropathology. Xenografts of HIV-1-infected human monocytes (placed into the putamen and cortex of SCID mice) remained viable for 5 weeks. HIV-1 p24 antigen expression in mouse brain was persistent. Progressive inflammatory responses (including astrogliosis and cytokine production), which began at 3 days, peaked at day 12. The range of astrocyte proliferative reactions exceeded the inoculation site by > 1000 microns. Brains with virus-infected monocytes showed a > or = 1.6-fold increase in glial fibrillary acidic protein (staining distribution and intensity) as compared with similarly inoculated brains with uninfected control monocytes. These findings paralleled the accumulation and activation of murine microglia (increased branching of cell processes, formation of microglial nodules, interleukin (IL)-1 beta and IL-6 expression). An inflammatory reaction of human monocytes (as defined by HLA-DR, IL-1 beta, IL-6, and tumor necrosis factor-alpha expression) and neuronal injury (apoptosis) also developed after virus-infected monocyte xenograft placement into mouse brain tissue. These data, taken together, demonstrate that this SCID mouse model of HIV-1 neuropathogenesis can reproduce key aspects of disease (virus-infected macrophages, astrocytosis, microglial activation, and neuronal damage). This model may serve as an important means for therapeutic development directed toward improving mental function in HIV-infected subjects with cognitive and motor dysfunction. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 14 Figure 15 PMID:8780406

  13. Landfill leachate-induced toxicity in mice.

    PubMed

    Bakare, A A; Mosuro, A A; Osibanjo, O

    2003-10-01

    Microbial, plant and studies in aquatic animals have shown that landfill leachate is toxic. However, more information about its effects in terrestrial animals is required. As a part of ongoing research into the toxic effects of landfill leachate in Nigeria, we evaluated the acute effects of raw and simulated leachates from Abadina, Orita-Aperin and Oworonsoki dump sites, all in Southwest Nigeria, in mice. Raw leachates were obtained directly from the dumps while the simulated leachates were obtained from the solid wastes in the laboratory by using the ASTM method. The samples were designated Abadina raw leachate (ARL), Orita-Aperin raw leachate (OARL) and Oworonsoki raw leachate (OWRL); and Abadina simulated leachate (ASL), Orita-Aperin simulated leachate (OASL) and Oworonsoki simulated leachate (OWSL). Their physico-chemical properties were determined in accordance with standard analytical methods. Young male mice (12-15 wk) weighing 24-31 g were exposed to 1%, 5%, 10%, 25%, 50% and 100% concentrations of each test samples for 5 consecutive days and were observed for a period of 96 h for toxic response. Mortality recorded at different times for each sample at the various concentrations was mostly within the last 48 h of the exposure period. The LC50 obtained are 100% for both ARL and OARL, and 50% for OWRL; and 83.50% and 50% for ASL and OWSL, respectively. It was indeterminate for OASL. Apart from this, other toxic effects like weight loss, sluggishness, loss of hair and reduced food intake were observed. The investigated samples were ranked as OWRL > OWSL > ASL > OARL > ARL > OASL. The observed effects were due to the toxic constituents present in the leachate samples. This suggests that the mixtures have the potential to cause harmful effect to public health and our environment through seepage into ground or surface water. PMID:15248658

  14. Oxytocin decreases sweet taste sensitivity in mice

    PubMed Central

    Sinclair, Michael S.; Perea-Martinez, Isabel; Abouyared, Marianne; St. John, Steven J.; Chaudhari, Nirupa

    2015-01-01

    Oxytocin (OXT) suppresses food intake and lack of OXT leads to overconsumption of sucrose. Taste bud cells were recently discovered to express OXT-receptor. In the present study we tested whether administering OXT to wild-type mice affects their licking behavior for tastants in a paradigm designed to be sensitive to taste perception. We injected C57BL/6J mice intraperitoneally (i.p.) with 10 mg/kg OXT and assayed their brief-access lick responses, motivated by water deprivation, to NaCl (300 mM), citric acid (20 mM), quinine (0.3 mM), saccharin (10 mM), and a mix of MSG and IMP (100 mM and 0.5 mM respectively). OXT had no effect on licking for NaCl, citric acid, or quinine. A possible effect of OXT on saccharin and MSG+IMP was difficult to interpret due to unexpectedly low lick rates to water (the vehicle for all taste solutions), likely caused by the use of a high OXT dose that suppressed licking and other behaviors. A subsequent experiment focused on another preferred tastant, sucrose, and employed a much lower OXT dose (0.1 mg/kg). This modification, based on our measurements of plasma OXT following i.p. injection, permitted us to elevate plasma [OXT] sufficiently to preferentially activate taste bud cells. OXT at this low dose significantly reduced licking responses to 0.3 M sucrose, and overall shifted the sucrose concentration – behavioral response curves rightward (mean EC50saline = 0.362 M vs. EC50OXT = 0.466 M). Males did not differ from females under any condition in this study. We propose that circulating oxytocin is another factor that modulates taste-based behavior. PMID:25554481

  15. Chronic Activation of FXR in Transgenic Mice Caused Perinatal Toxicity and Sensitized Mice to Cholesterol Toxicity

    PubMed Central

    Cheng, Qiuqiong; Inaba, Yuka; Lu, Peipei; Xu, Meishu; He, Jinhan; Zhao, Yueshui; Guo, Grace L.; Kuruba, Ramalinga; de la Vega, Rona; Evans, Rhobert W.; Li, Song

    2015-01-01

    The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage. PMID:25719402

  16. Effects of chronic doxepin and amitriptyline administration in nave mice and in neuropathic pain mice model.

    PubMed

    Mika, J; Jurga, A M; Starnowska, J; Wasylewski, M; Rojewska, E; Makuch, W; Kwiatkowski, K; Malek, N; Przewlocka, B

    2015-05-21

    Neuropathic pain is a severe clinical problem, often appearing as a co-symptom of many diseases or manifesting as a result of damage to the nervous system. Many drugs and agents are currently used for the treatment of neuropathic pain, such as tricyclic antidepressants (TCAs). The aims of this paper were to test the effects of two classic TCAs, doxepin and amitriptyline, in nave animals and in a model of neuropathic pain and to determine the role of cytokine activation in the effects of these drugs. All experiments were carried out with Albino-Swiss mice using behavioral tests (von Frey test and the cold plate test) and biochemical analyses (qRT-PCR and Western blot). In the mice subjected to chronic constriction injury (CCI), doxepin and amitriptyline attenuated the symptoms of neuropathic pain and diminished the CCI-induced increase in the levels of spinal interleukin (IL)-6 and -1? mRNA, but not the protein levels of these cytokines, measured on day 12. Unexpectedly, chronic administration of doxepin or amitriptyline for 12 days produced allodynia and hyperalgesia in nave mice. The treatment with these drugs did not influence the spinal levels of IL-1? and IL-6 mRNA, however, the protein levels of these pronociceptive factors were increased. The administration of ondansetron (5-HT3 receptor antagonist) significantly weakened the allodynia and hyperalgesia induced by both antidepressants in nave mice; in contrast, yohimbine (?2-adrenergic receptors antagonist) did not influence these effects. Allodynia and hyperalgesia induced in nave animals by amitriptyline and doxepin may be associated with an increase in the levels of pronociceptive cytokines resulting from 5-HT3-induced hypersensitivity. Our results provide new and important information about the possible side effects of antidepressants. Further investigation of these mechanisms may help to guide decisions about the use of classic TCAs for therapy. PMID:25769941

  17. The gut microbiota modulates host energy and lipid metabolism in mice[S

    PubMed Central

    Velagapudi, Vidya R.; Hezaveh, Rahil; Reigstad, Christopher S.; Gopalacharyulu, Peddinti; Yetukuri, Laxman; Islam, Sama; Felin, Jenny; Perkins, Rosie; Borén, Jan; Orešič, Matej; Bäckhed, Fredrik

    2010-01-01

    The gut microbiota has recently been identified as an environmental factor that may promote metabolic diseases. To investigate the effect of gut microbiota on host energy and lipid metabolism, we compared the serum metabolome and the lipidomes of serum, adipose tissue, and liver of conventionally raised (CONV-R) and germ-free mice. The serum metabolome of CONV-R mice was characterized by increased levels of energy metabolites, e.g., pyruvic acid, citric acid, fumaric acid, and malic acid, while levels of cholesterol and fatty acids were reduced. We also showed that the microbiota modified a number of lipid species in the serum, adipose tissue, and liver, with its greatest effect on triglyceride and phosphatidylcholine species. Triglyceride levels were lower in serum but higher in adipose tissue and liver of CONV-R mice, consistent with increased lipid clearance. Our findings show that the gut microbiota affects both host energy and lipid metabolism and highlights its role in the development of metabolic diseases. PMID:20040631

  18. Cardiovascular manifestations of renovascular hypertension in diabetic mice

    PubMed Central

    Kashyap, Sonu; Engel, Sean; Osman, Mazen; Al-Saiegh, Yousif; Wongjarupong, Asarn

    2016-01-01

    Purpose. Type 2 diabetes is the leading cause of end stage renal disease in the United States. Atherosclerotic renal artery stenosis is commonly observed in diabetic patients and impacts the rate of renal and cardiovascular disease progression. We sought to test the hypothesis that renovascular hypertension, induced by unilateral renal artery stenosis, exacerbates cardiac remodeling in leptin-deficient (db/db) mice, which serves as a model of human type II diabetes. Methods. We employed a murine model of renovascular hypertension through placement of a polytetrafluoroethylene cuff on the right renal artery in db/db mice. We studied 109 wild-type (non-diabetic, WT) and 95 db/db mice subjected to renal artery stenosis (RAS) or sham surgery studied at 1, 2, 4, and 6+ weeks following surgery. Cardiac remodeling was assessed by quantitative analysis of the percent of myocardial surface area occupied by interstitial fibrosis tissue, as delineated by trichrome stained slides. Aortic pathology was assessed by histologic sampling of grossly apparent structural abnormalities or by section of ascending aorta of vessels without apparent abnormalities. Results. We noted an increased mortality in db/db mice subjected to RAS. The mortality rate of db/db RAS mice was about 23.5%, whereas the mortality rate of WT RAS mice was only 1.5%. Over 60% of mortality in the db/db mice occurred in the first two weeks following RAS surgery. Necropsy showed massive intrathoracic hemorrhage associated with aortic dissection, predominantly in the ascending aorta and proximal descending aorta. Aortas from db/db RAS mice showed more smooth muscle dropout, loss of alpha smooth muscle actin expression, medial disruption, and hemorrhage than aortas from WT mice with RAS. Cardiac tissue from db/db RAS mice had more fibrosis than did cardiac tissue from WT RAS mice. Conclusions. db/db mice subjected to RAS are prone to develop fatal aortic dissection, which is not observed in WT mice with RAS. The db/db RAS model provides the basis for future studies directed towards defining basic mechanisms underlying the interaction of hypertension and diabetes on the development of aortic lesions. PMID:26925344

  19. Mice Do Not Habituate to Metabolism Cage Housing–A Three Week Study of Male BALB/c Mice

    PubMed Central

    Kalliokoski, Otto; Jacobsen, Kirsten R.; Darusman, Huda S.; Henriksen, Trine; Weimann, Allan; Poulsen, Henrik E.; Hau, Jann; Abelson, Klas S. P.

    2013-01-01

    The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in feces throughout the study when compared to controls. Urinary biomarkers confirmed that these mice suffered from elevated levels of oxidative stress, and increased creatinine excretions indicated increased muscle catabolism. Changes in the core body temperature (stress-induced hyperthermia) and the fur state of the mice also indicated impaired well-being in the metabolism cage housed mice. However, monitoring body weight and feed intake was found misleading in assessing the wellbeing of mice over a longer time course, and the forced swim test was found poorly suited for studying chronic stress in mice in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased overall metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology. PMID:23505511

  20. Nonlinear Pharmacokinetics of 5-Methoxy-N,N-dimethyltryptamine in MiceS?

    PubMed Central

    Shen, Hong-Wu; Jiang, Xi-Ling

    2011-01-01

    5-Methoxy-N,N,-dimethyltryptamine (5-MeO-DMT), an abused serotonergic indolealkylamine drug, was placed into Schedule I controlled substance status in the United States as of January 19, 2011. In previous studies, we have shown the impact of monoamine oxidase A and cytochrome P450 2D6 enzymes on 5-MeO-DMT metabolism and pharmacokinetics. The aim of this study was to investigate 5-MeO-DMT pharmacokinetic properties after intravenous or intraperitoneal administration of three different doses (2, 10, and 20 mg/kg) to CYP2D6-humanized (Tg-CYP2D6) and wild-type control mice. Systemic exposure [area under the curve (AUC)] to 5-MeO-DMT was increased nonproportionally with the increase in dose. The existence of nonlinearity in serum 5-MeO-DMT pharmacokinetics was clearly manifested by dose-normalized AUC values, which were approximately 1.5- to 2.0-fold (intravenous) and 1.8- to 2.7-fold (intraperitoneal) higher in wild-type or Tg-CYP2D6 mice dosed with 10 and 20 mg/kg 5-MeO-DMT, respectively, than those in mice treated with 2 mg/kg 5-MeO-DMT. Furthermore, a two-compartment model including first-order absorption, nonlinear (Michaelis-Menten) elimination, and CYP2D6-dependent linear elimination from the central compartment was developed to characterize the intravenous and intraperitoneal pharmacokinetic data for 5-MeO-DMT in wild-type and Tg-CYP2D6 mice. In addition, 5-MeO-DMT was readily detected in mouse brain after drug treatment, and brain 5-MeO-DMT concentrations were also increased nonproportionally with the increase of dose. The results establish a nonlinear pharmacokinetic property for 5-MeO-DMT in mice, suggesting that the risk of 5-MeO-DMT intoxication may be increased nonproportionally at higher doses. PMID:21464174

  1. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.

    PubMed

    Trammell, Samuel A J; Weidemann, Benjamin J; Chadda, Ankita; Yorek, Matthew S; Holmes, Amey; Coppey, Lawrence J; Obrosov, Alexander; Kardon, Randy H; Yorek, Mark A; Brenner, Charles

    2016-01-01

    Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies. PMID:27230286

  2. Abnormal regulation of TSG101 in mice with spongiform neurodegeneration

    PubMed Central

    Jiao, Jian; Sun, Kaihua; Walker, Will P.; Bagher, Pooneh; Cota, Christina D.; Gunn, Teresa M.

    2009-01-01

    Summary Spongiform neurodegeneration is characterized by the appearance of vacuoles throughout the central nervous system. It has many potential causes, but the underlying cellular mechanisms are not well understood. Mice lacking the E3 ubiquitin ligase Mahogunin Ring Finger-1 (MGRN1) develop age-dependent spongiform encephalopathy. We identified an interaction between a “PSAP” motif in MGRN1 and the ubiquitin E2 variant (UEV) domain of TSG101, a component of the endosomal sorting complex required for transport I (ESCRT-I), and demonstrate that MGRN1 multimonoubiquitinates TSG101. We examined the in vivo consequences of loss of MGRN1 on TSG101 expression and function in the mouse brain. The pattern of TSG101 ubiquitination differed in the brains of wild-type mice and Mgrn1 null mutant mice: at 1 month of age, null mutant mice had less ubiquitinated TSG101, while in adults, mutant mice had more ubiquitinated, insoluble TSG101 than wild-type mice. There was an associated increase in epidermal growth factor receptor (EGFR) levels in mutant brains. These results suggest that loss of MGRN1 promotes ubiquitination of TSG101 by other E3s and may prevent its disassociation from endosomal membranes or cause it to form insoluble aggregates. Our data implicate loss of normal TSG101 function in endo-lysosomal trafficking in the pathogenesis of spongiform neurodegeneration in Mgrn1 null mutant mice. PMID:19703557

  3. Assessment of Dental Fluorosis in Mmp20+/− Mice

    PubMed Central

    Sharma, R.; Tye, C.E.; Arun, A.; MacDonald, D.; Chatterjee, A.; Abrazinski, T.; Everett, E.T.; Whitford, G.M.; Bartlett, J.D.

    2011-01-01

    The molecular mechanisms that underlie dental fluorosis are poorly understood. The retention of enamel proteins hallmarking fluorotic enamel may result from impaired hydrolysis and/or removal of enamel proteins. Previous studies have suggested that partial inhibition of Mmp20 expression is involved in the etiology of dental fluorosis. Here we ask if mice expressing only one functional Mmp20 allele are more susceptible to fluorosis. We demonstrate that Mmp20+/− mice express approximately half the amount of MMP20 as do wild-type mice. The Mmp20 heterozygous mice have normal-appearing enamel, with Vickers microhardness values similar to those of wild-type control enamel. Therefore, reduced MMP20 expression is not solely responsible for dental fluorosis. With 50-ppm-fluoride (F−) treatment ad libitum, the Mmp20+/− mice had F− tissue levels similar to those of Mmp20+/+ mice. No significant difference in enamel hardness was observed between the F−-treated heterozygous and wild-type mice. Interestingly, we did find a small but significant difference in quantitative fluorescence between these two groups, which may be attributable to slightly higher protein content in the Mmp20+/− mouse enamel. We conclude that MMP20 plays a nominal role in dental enamel fluorosis. PMID:21386097

  4. Subchronic exposure of mice to Love Canal soil contaminants

    SciTech Connect

    Silkworth, J.B.; McMartin, D.N.; Rej, R.; Narang, R.S.; Stein, V.B.; Briggs, R.G.; Kaminsky, L.S.

    1984-04-01

    The health hazard potential of soil collected from the surface of the Love Canal chemical dump site in Niagara Falls, New York, was assessed in 90-day exposure studies. Female CD-1 mice were exposed to two concentrations of the volatile components of 1 kg of soil with and without direct soil contact. Control mice were identically housed but without soil. The soil was replaced weekly and 87 compounds were detected in the air in the cages above fresh and 7-day-old soil as analyzed by gas chromatography/mass spectrometry. The concentration of many of these compounds decreased during the 7-day exposure cycle. Histopathologic, hematologic, and serum enzyme studies followed necropsy of all mice. There was no mortality of mice exposed for up to 90 days under any condition. Thymus and spleen weights relative to body weight were increased after 4 weeks of exposure by inhalation but not after 8 or 12 weeks of exposure. alpha-, beta-, and delta- Benzenehexachlorides , pentachlorobenzene, and hexachlorobenzene were detected in liver tissue from these animals. Mice exposed to 5- to 10-fold elevated concentration of volatiles had increased body and relative kidney weights. There was no chemically induced lesion in any animal exposed only to the volatile soil contaminants. Mice exposed by direct contact with the soil without elevated volatile exposure had increased body (10%) and relative liver weights (169%). Centrolobular hepatocyte hypertrophy, which involved 40 to 70% of the lobules, was observed in all mice in this group.

  5. Inflammatory responses to acute pneumovirus infection in neonatal mice

    PubMed Central

    2010-01-01

    Background The innate immune responses of neonates differ dramatically from those of adults. Here we examine the acute inflammatory responses of neonatal and weanling mice infected with pneumonia virus of mice (PVM), a rodent pathogen (family Paramyxoviridae, genus Pneumovirus) that replicates the sequelae of severe respiratory syncytial virus infection. Results We demonstrate that virus replication proceeds indistinguishably in all age groups (inoculated at 1, 2, 3 and 4 weeks of age), although inflammatory responses vary in extent and character. Some of the biochemical mediators detected varied minimally with age at inoculation. Most of the mediators evaluated demonstrated elevated expression over baseline correlating directly with age at the time of virus inoculation. Among the latter group are CCL2, CCL3, and IFN-γ, all cytokines previously associated with PVM-induced inflammatory pathology in mature mice. Likewise, we detect neutrophil recruitment to lung tissue in all age groups, but recruitment is most pronounced among the older (3 - 4 week old) mice. Interestingly, all mice exhibit failure to thrive, lagging in expected weight gain for given age, including the youngest mice that present little overt evidence of inflammation. Conclusions Our findings among the youngest mice may explain in part the phenomenon of atypical or minimally symptomatic respiratory infections in human neonates, which may be explored further with this infection model. PMID:21078159

  6. Generation and analysis of mice lacking the chemokine fractalkine.

    PubMed

    Cook, D N; Chen, S C; Sullivan, L M; Manfra, D J; Wiekowski, M T; Prosser, D M; Vassileva, G; Lira, S A

    2001-05-01

    Fractalkine (CX(3)CL1) is the first described chemokine that can exist either as a soluble protein or as a membrane-bound molecule. Both forms of fractalkine can mediate adhesion of cells expressing its receptor, CX(3)CR1. This activity, together with its expression on endothelial cells, suggests that fractalkine might mediate adhesion of leukocytes to the endothelium during inflammation. Fractalkine is also highly expressed in neurons, and its receptor, CX(3)CR1, is expressed on glial cells. To determine the biologic role of fractalkine, we used targeted gene disruption to generate fractalkine-deficient mice. These mice did not exhibit overt behavioral abnormalities, and histologic analysis of their brains did not reveal any gross changes compared to wild-type mice. In addition, these mice had normal hematologic profiles except for a decrease in the number of blood leukocytes expressing the cell surface marker F4/80. The cellular composition of their lymph nodes did not differ significantly from that of wild-type mice. Similarly, the responses of fractalkine(-/-) mice to a variety of inflammatory stimuli were indistinguishable from those of wild-type mice. PMID:11287620

  7. Generation and Analysis of Mice Lacking the Chemokine Fractalkine

    PubMed Central

    Cook, Donald N.; Chen, Shu-Cheng; Sullivan, Lee M.; Manfra, Denise J.; Wiekowski, Maria T.; Prosser, Dina M.; Vassileva, Galya; Lira, Sergio A.

    2001-01-01

    Fractalkine (CX3CL1) is the first described chemokine that can exist either as a soluble protein or as a membrane-bound molecule. Both forms of fractalkine can mediate adhesion of cells expressing its receptor, CX3CR1. This activity, together with its expression on endothelial cells, suggests that fractalkine might mediate adhesion of leukocytes to the endothelium during inflammation. Fractalkine is also highly expressed in neurons, and its receptor, CX3CR1, is expressed on glial cells. To determine the biologic role of fractalkine, we used targeted gene disruption to generate fractalkine-deficient mice. These mice did not exhibit overt behavioral abnormalities, and histologic analysis of their brains did not reveal any gross changes compared to wild-type mice. In addition, these mice had normal hematologic profiles except for a decrease in the number of blood leukocytes expressing the cell surface marker F4/80. The cellular composition of their lymph nodes did not differ significantly from that of wild-type mice. Similarly, the responses of fractalkine−/− mice to a variety of inflammatory stimuli were indistinguishable from those of wild-type mice. PMID:11287620

  8. Characteristics of Skeletal Muscle Fibers of SOD1 Knockout Mice.

    PubMed

    Nagahisa, Hiroshi; Okabe, Kazuma; Iuchi, Yoshihito; Fujii, Junichi; Miyata, Hirofumi

    2016-01-01

    Cu/Zn superoxide dismutase (SOD1) knockout (KO) mice are known as an aging model in some aspects, but the damage and regeneration process of each fiber type have not been sufficiently studied. In this study, we investigated the damage and satellite cell state of the gastrocnemius muscle in SOD1 KO mice (6 months old) using immunohistochemical staining and real-time RT-PCR. The proportion of central nuclei-containing Type IIx/b fibers in the deep and superficial portions of the gastrocnemius muscle was significantly higher in SOD1 KO than control mice. The number of satellite cells per muscle fiber decreased in all muscle fiber types in the deep portion of the gastrocnemius muscle in SOD1 KO mice. In addition, the mRNA expression levels of Pax7 and myogenin, which are expressed in satellite cells in the activation, proliferation, and differentiation states, significantly increased in the gastrocnemius muscle of SOD1 KO mice. Furthermore, mRNA of myosin heavy chain-embryonic, which is expressed in the early phase of muscle regeneration, significantly increased in SOD1 KO mice. It was suggested that muscle is damaged by reactive oxygen species produced in the mitochondrial intermembrane space in Type IIxb fibers, accelerating the proliferation and differentiation of satellite cells through growth factors in SOD1 KO mice. PMID:26798428

  9. Oxidative Stress-Dependent Coronary Endothelial Dysfunction in Obese Mice

    PubMed Central

    Gamez-Mendez, Ana María; Vargas-Robles, Hilda; Ríos, Amelia; Escalante, Bruno

    2015-01-01

    Obesity is involved in several cardiovascular diseases including coronary artery disease and endothelial dysfunction. Endothelial Endothelium vasodilator and vasoconstrictor agonists play a key role in regulation of vascular tone. In this study, we evaluated coronary vascular response in an 8 weeks diet-induced obese C57BL/6 mice model. Coronary perfusion pressure in response to acetylcholine in isolated hearts from obese mice showed increased vasoconstriction and reduced vasodilation responses compared with control mice. Vascular nitric oxide assessed in situ with DAF-2 DA showed diminished levels in coronary arteries from obese mice in both basal and acetylcholine-stimulated conditions. Also, released prostacyclin was decreased in heart perfusates from obese mice, along with plasma tetrahydrobiopterin level and endothelium nitric oxide synthase dimer/monomer ratio. Obesity increased thromboxane A2 synthesis and oxidative stress evaluated by superoxide and peroxynitrite levels, compared with control mice. Obese mice treated with apocynin, a NADPH oxidase inhibitor, reversed all parameters to normal levels. These results suggest that after 8 weeks on a high-fat diet, the increase in oxidative stress lead to imbalance in vasoactive substances and consequently to endothelial dysfunction in coronary arteries. PMID:26381906

  10. Immunomodulatory and antioxidative activity of Cordyceps militaris polysaccharides in mice.

    PubMed

    Liu, Jing-Yu; Feng, Cui-Ping; Li, Xing; Chang, Ming-Chang; Meng, Jun-Long; Xu, Li-Jing

    2016-05-01

    To evaluate the immune activation and reactive oxygen species scavenging activity of Cordyceps militaris polysaccharides (CMP) in vivo, 24 male and 24 female Kunming mice were randomly divided into four groups. The mice in the four experimental groups were administered 0 (normal control), 50, 100, or 200mg/kg/d body weight CMP via gavage. After 30 days, the viscera index, leukocyte count, differential leukocyte count, immunoglobulin (IgG) levels, and biochemical parameters were measured. The effect of CMP on the expression of tumor necrosis (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β in the spleens of experimental mice was investigated by real-time polymerase chain reaction. The results showed that the administration of CMP improved the immune function in mice, significantly increased the spleen and thymus indices, the spleen lymphocyte activity, the total quantity of white blood cells, and IgG function in mice serum. CMP exhibited significant antioxidative activity in mice, and decreased malondialdehyde levels in vivo. CMP upregulated the expression of TNF-α, IFN-γ, and IL-1β mRNA in high-dose groups compared to that observed for the control mice. We can thus conclude that CMP effectively improved the immune function through protection against oxidative stress. CMP thus shows potential for development as drugs and health supplements. PMID:26853825

  11. Characteristics of Skeletal Muscle Fibers of SOD1 Knockout Mice

    PubMed Central

    Nagahisa, Hiroshi; Okabe, Kazuma; Iuchi, Yoshihito; Fujii, Junichi; Miyata, Hirofumi

    2016-01-01

    Cu/Zn superoxide dismutase (SOD1) knockout (KO) mice are known as an aging model in some aspects, but the damage and regeneration process of each fiber type have not been sufficiently studied. In this study, we investigated the damage and satellite cell state of the gastrocnemius muscle in SOD1 KO mice (6 months old) using immunohistochemical staining and real-time RT-PCR. The proportion of central nuclei-containing Type IIx/b fibers in the deep and superficial portions of the gastrocnemius muscle was significantly higher in SOD1 KO than control mice. The number of satellite cells per muscle fiber decreased in all muscle fiber types in the deep portion of the gastrocnemius muscle in SOD1 KO mice. In addition, the mRNA expression levels of Pax7 and myogenin, which are expressed in satellite cells in the activation, proliferation, and differentiation states, significantly increased in the gastrocnemius muscle of SOD1 KO mice. Furthermore, mRNA of myosin heavy chain-embryonic, which is expressed in the early phase of muscle regeneration, significantly increased in SOD1 KO mice. It was suggested that muscle is damaged by reactive oxygen species produced in the mitochondrial intermembrane space in Type IIxb fibers, accelerating the proliferation and differentiation of satellite cells through growth factors in SOD1 KO mice. PMID:26798428

  12. Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma.

    PubMed

    Miller, Cassandra L; Muthupalani, Sureshkumar; Shen, Zeli; Drees, Frauke; Ge, Zhongming; Feng, Yan; Chen, Xiaowei; Gong, Guanyu; Nagar, Karan K; Wang, Timothy C; Gertler, Frank B; Fox, James G

    2016-01-01

    During a survey of clinical rectal prolapse (RP) cases in the mouse population at MIT animal research facilities, a high incidence of RP in the lamellipodin knock-out strain, C57BL/6-Raph1tm1Fbg (Lpd-/-) was documented. Upon further investigation, the Lpd-/- colony was found to be infected with multiple endemic enterohepatic Helicobacter species (EHS). Lpd-/- mice, a transgenic mouse strain produced at MIT, have not previously shown a distinct immune phenotype and are not highly susceptible to other opportunistic infections. Predominantly male Lpd-/- mice with RP exhibited lesions consistent with invasive rectal carcinoma concomitant to clinically evident RP. Multiple inflammatory cytokines, CD11b+Gr1+ myeloid-derived suppressor cell (MDSC) populations, and epithelial cells positive for a DNA damage biomarker, H2AX, were elevated in affected tissue, supporting their role in the neoplastic process. An evaluation of Lpd-/- mice with RP compared to EHS-infected, but clinically normal (CN) Lpd-/- animals indicated that all of these mice exhibit some degree of lower bowel inflammation; however, mice with prolapses had significantly higher degree of focal lesions at the colo-rectal junction. When Helicobacter spp. infections were eliminated in Lpd-/- mice by embryo transfer rederivation, the disease phenotype was abrogated, implicating EHS as a contributing factor in the development of rectal carcinoma. Here we describe lesions in Lpd-/- male mice consistent with a focal inflammation-induced neoplastic transformation and propose this strain as a mouse model of rectal carcinoma. PMID:27045955

  13. Experimental autoimmune orchitis in T-cell-deficient mice.

    PubMed

    Bernard, C C; Mitchell, G F; Leydon, J; Bargerbos, A

    1978-01-01

    Experimental autoimmune orchitis (EAO) was induced in inbred strains of mice by injection of mouse testis homogenate (MTH) in Freund's complete adjuvant with pertussis vaccine. Although all mice injected with MTH and adjuvants developed signs of EAO, there were marked strain variations in susceptibility to EAO suggesting that genetic factors may be involved in the response to antigen or to adjuvants. Studies in hypothymic BALB/c. nu/nu mice indicated that a source of T cell was required for induction of EAO. Thus BALB/c. nu/nu mice were not able to develop EAO, despite adequate orchitogenic challenge; reconstitution of nu/nu mice with syngeneic thymocytes completely restored the capacity of such mice to develop orchitis. Transfer of EAO was effected in nu/nu mice with lymphoid cells from appropriately immunized donors but not with immune serum. However, both T cells and antibodies may be necessary in the effector stages of the disease since the capacity of lymphoid cells to transfer EAO was only partially inhibited by anti-Thy-1.2 treatment. PMID:304445

  14. Effects of Hindlimb Unweighting on Arterial Contractile Responses in Mice

    NASA Technical Reports Server (NTRS)

    Ma, Jia; Ren, Xin-Ling; Purdy, Ralph E.

    2003-01-01

    The aim of this work was to determine if hindlimb unweighting in mice alters arterial contractile responses. Sixteen male C57B/6 mice and 16 male Chinese Kunming mice were divided into control and 3 weeks hindlimb unweighting groups, respectively. Using isolated arterial rings from different arteries of mouse, effects of 3 weeks hindlimb unweighting on arterial contractile responsiveness were examined in vitro. The results showed that, in arterial rings from both C57B/6 and Chinese Kunming mice, maximum isometric contractile tensions evoked by either KCl or phenylephrine were significantly lower in abdominal aortic, mesenteric arterial and femoral arterial rings from hindlimb unweighting, compared to control mice. However, the maximal contractile responses of common carotid rings to KCl and PE were not significantly different between control and hindlimb unweighting groups. The sensitivity (EC(sub 50)) of all arteries to KCl or PE showed no significant differences between control and hindlimb unweighting mice. These data indicated that 3 weeks hindlimb unweighting results in a reduced capacity of the arterial smooth muscle of the hindquarter to develop tension. In addition, the alterations in arterial contractile responses caused by hindlimb unweighting in mice are similar as those in rats. Our work suggested that hindlimb unweighting mouse model may be used as a model for the study of postflight cardiovascular deconditioning.

  15. Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma

    PubMed Central

    Miller, Cassandra L.; Muthupalani, Sureshkumar; Shen, Zeli; Drees, Frauke; Ge, Zhongming; Feng, Yan; Chen, Xiaowei; Gong, Guanyu; Nagar, Karan K.; Wang, Timothy C.; Gertler, Frank B.; Fox, James G.

    2016-01-01

    During a survey of clinical rectal prolapse (RP) cases in the mouse population at MIT animal research facilities, a high incidence of RP in the lamellipodin knock-out strain, C57BL/6-Raph1tm1Fbg (Lpd-/-) was documented. Upon further investigation, the Lpd-/- colony was found to be infected with multiple endemic enterohepatic Helicobacter species (EHS). Lpd-/- mice, a transgenic mouse strain produced at MIT, have not previously shown a distinct immune phenotype and are not highly susceptible to other opportunistic infections. Predominantly male Lpd-/- mice with RP exhibited lesions consistent with invasive rectal carcinoma concomitant to clinically evident RP. Multiple inflammatory cytokines, CD11b+Gr1+ myeloid-derived suppressor cell (MDSC) populations, and epithelial cells positive for a DNA damage biomarker, H2AX, were elevated in affected tissue, supporting their role in the neoplastic process. An evaluation of Lpd-/- mice with RP compared to EHS-infected, but clinically normal (CN) Lpd-/- animals indicated that all of these mice exhibit some degree of lower bowel inflammation; however, mice with prolapses had significantly higher degree of focal lesions at the colo-rectal junction. When Helicobacter spp. infections were eliminated in Lpd-/- mice by embryo transfer rederivation, the disease phenotype was abrogated, implicating EHS as a contributing factor in the development of rectal carcinoma. Here we describe lesions in Lpd-/- male mice consistent with a focal inflammation-induced neoplastic transformation and propose this strain as a mouse model of rectal carcinoma. PMID:27045955

  16. Granuloma Formation Induced in Mice by Chemically Defined Mycobacterial Fractions

    PubMed Central

    Bekierkunst, A.; Levij, I. S.; Yarkoni, E.; Vilkas, E.; Adam, A.; Lederer, E.

    1969-01-01

    Amounts of trehalose-6,6-dimycolate as small as 1 to 5 ?g can, after intravenous injection, induce in the lungs of mice formation of tubercles in which the cellular composition is indistinguishable from that in tubercles formed after an infection with living BCG bacilli. The strongest cellular response in mice was induced by cord factor from Mycobacterium kansasii; the weakest was induced by cord factor from the BCG strain of M. bovis. It was found that three intravenous injections of cord factor induced a more extensive cellular response than did one injection of the same total amount of cord factor. Mice treated intravenously with cord factor were protected against an intravenous challenge with the virulent H37Rv strain of M. tuberculosis. The cellular response in the lungs of mice to intraperitoneal injections of living BCG and cord factor was very weak compared with that after intravenous injections. Intraperitoneal vaccination of mice with cord factor did not protect the mice against a challenge with virulent tubercle bacilli. Mice vaccinated intraperitoneally with BCG were immunized although no granulomas, or very few, were present in the lungs at the time of the challenge. The significance of the cellular response induced by cord factor is discussed. Images PMID:4981067

  17. Experimental sialodacryoadenitis virus infection in athymic CD-1 mice.

    PubMed Central

    Percy, D H; Bond, S J; MacInnes, J I; Descôteaux, J P

    1988-01-01

    The purpose of the study was to investigate the susceptibility of nude mice to sialodacryoadenitis virus. Young adult male CD-1 nude mice were inoculated intranasally with virus, killed at 2, 4, 6, 8, 10 and 20 days postinoculation and examined for virus-induced lesions in tissues including respiratory tract. Inoculated and control mice were examined by virus isolation and serology. In a companion study, male Wistar rats were inoculated intranasally with the same inoculum, and examined by histopathology, immunofluorescence microscopy and serology. In virus-inoculated mice, lesions were minimal in the lower respiratory tract, and were absent in other tissues. Virus was isolated from the lower respiratory tract in animals sampled at six or eight days postinoculation. Antiviral antibody was not detected in sera from inoculated and control mice. Virus-associated lesions and antibodies were readily detected in rats following inoculation. Based on this study, there is no evidence that inadvertent exposure to sialodacryoadenitis virus should pose a threat to CD-1 nude mice, and their susceptibility to the disease appears to be similar to that reported in euthymic CD-1 mice. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2844379

  18. Abnormal antioxidant defence in some tissues of congenitally obese mice.

    PubMed Central

    Capel, I D; Dorrell, H M

    1984-01-01

    The concentration of lipoperoxides (estimated as thiobarbituric acid-reactive material) and some components of the antioxidant defence system have been compared in various tissues of lean and congenitally obese mice. NADPH-stimulated lipoperoxide generation in vitro was significantly higher in microsomes (microsomal fractions) prepared from obese hepatic tissue than lean. Plasma, liver and brain lipoperoxide concentration was significantly higher in obese mice. In blood derived from obese mice the concentration of non-enzymic antioxidants including caeruloplasmin and vitamin A was higher, but hepatic retinol concentration was lower in these animals. In all the tissues assayed the glutathione peroxidase activity against H2O2 was less than its activity against cumene hydroperoxide. Assayed with either substrate, glutathione peroxidase activity was significantly higher in the brain and blood of obese mice than their lean counterparts. Conversely, liver glutathione peroxidase was decreased in obese animals, representing 43% of the activity of the lean-mouse liver enzyme against H2O2 and 81% of the cumene hydroperoxide-reducing activity. The liver of obese mice had significantly less, and the kidneys more, oxidized glutathione than the corresponding tissues of lean mice. Further investigations on hepatic tissue indicated that glutathione reductase activity was lower in the obese animals, but there was no significant difference between glucose-6-phosphate dehydrogenase activity in obese and lean mice. PMID:6721863

  19. Social experience alters the response to social stress in mice.

    PubMed

    Avitsur, Ronit; Stark, Jennifer L; Dhabhar, Firdaus S; Kramer, Kari A; Sheridan, John F

    2003-12-01

    Individual differences in the response to stressful stimuli have been documented in humans and in a variety of animal species. Recently, we demonstrated that social stress induced a state of glucocorticoid (GC) resistance in mouse splenocytes, however this response was highly variable among cage mates. Since these studies were conducted using inbred mice (C57BL/6), it was suggested that environmental factors were the source of this variability. The following study examined possible factors that may have contributed to the development of individual differences in the susceptibility of mice to social stress. First, the effect of rearing conditions was studied by comparing the development of GC resistance in mice reared in isolation or in groups. In addition, the effect of previous social experiences was studied in mice that were re-housed to facilitate the formation of new social hierarchies in the cages. The results indicated that isolation altered the behavior of the mice during the social stress, but did not affect the development of GC resistance in response to the stress. Re-housing and the resulting loss of social status increased the susceptibility of mice to the development of GC resistance following social stress. Together, these findings indicate that environmental factors, such as previous social experiences, may alter the susceptibility to the effects of future social stress in inbred mice. PMID:14583234

  20. Serotonin deficiency exacerbates acetaminophen-induced liver toxicity in mice.

    PubMed

    Zhang, Jingyao; Song, Sidong; Pang, Qing; Zhang, Ruiyao; Zhou, Lei; Liu, Sushun; Meng, Fandi; Wu, Qifei; Liu, Chang

    2015-01-01

    Acetaminophen (APAP) overdose is a major cause of acute liver failure. Peripheral 5-hydroxytryptamine (serotonin, 5-HT) is a cytoprotective neurotransmitter which is also involved in the hepatic physiological and pathological process. This study seeks to investigate the mechanisms involved in APAP-induced hepatotoxicity, as well as the role of 5-HT in the liver's response to APAP toxicity. We induced APAP hepatotoxicity in mice either sufficient of serotonin (wild-type mice and TPH1-/- plus 5- Hydroxytryptophan (5-HTP)) or lacking peripheral serotonin (Tph1-/- and wild-type mice plus p-chlorophenylalanine (PCPA)). Mice with sufficient 5-HT exposed to acetaminophen have a significantly lower mortality rate and a better outcome compared with mice deficient of 5-HT. This difference is at least partially attributable to a decreased level of inflammation, oxidative stress and endoplasmic reticulum (ER) stress, Glutathione (GSH) depletion, peroxynitrite formation, hepatocyte apoptosis, elevated hepatocyte proliferation, activation of 5-HT2B receptor, less activated c-Jun NH₂-terminal kinase (JNK) and hypoxia-inducible factor (HIF)-1α in the mice sufficient of 5-HT versus mice deficient of 5-HT. We thus propose a physiological function of serotonin that serotonin could ameliorate APAP-induced liver injury mainly through inhibiting hepatocyte apoptosis ER stress and promoting liver regeneration. PMID:25631548

  1. In Vivo image Analysis Using iRFP Transgenic Mice

    PubMed Central

    Tran, Mai Thi Nhu; Tanaka, Junko; Hamada, Michito; Sugiyama, Yuka; Sakaguchi, Shota; Nakamura, Megumi; Takahashi, Satoru; Miwa, Yoshihiro

    2014-01-01

    Fluorescent proteins with light wavelengths within the optical window are one of the improvements in in vivo imaging techniques. Near-infrared (NIR) fluorescent protein (iRFP) is a stable, nontoxic protein that emits fluorescence within the NIR optical window without the addition of exogenous substrate. However, studies utilizing an in vivo iRFP model have not yet been published. Here, we report the generation of transgenic iRFP mice with ubiquitous NIR fluorescence expression. iRFP expression was observed in approximately 50% of the offspring from a matings between iRFP transgenic and WT mice. The serum and blood cell indices and body weights of iRFP mice were similar to those of WT mice. Red fluorescence with an excitation wavelength of 690 nm and an emission wavelength of 713 nm was detected in both newborn and adult iRFP mice. We also detected fluorescence emission in whole organs of the iRFP mice, including the brain, heart, liver, kidney, spleen, lung, pancreas, bone, testis, thymus, and adipose tissue. Therefore, iRFP transgenic mice may therefore be a useful tool for various types of in vivo imaging. PMID:25077761

  2. Resveratrol Protects the Brain of Obese Mice from Oxidative Damage

    PubMed Central

    Rege, Shraddha D.; Kumar, Sruthi; Wilson, David N.; Tamura, Leslie; Geetha, Thangiah; Mathews, Suresh T.; Huggins, Kevin W.; Broderick, Tom L.; Babu, Jeganathan Ramesh

    2013-01-01

    Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenolic phytoalexin that exerts cardioprotective, neuroprotective, and antioxidant effects. Recently it has been shown that obesity is associated with an increase in cerebral oxidative stress levels, which may enhance neurodegeneration. The present study evaluates the neuroprotective action of resveratrol in brain of obese (ob/ob) mice. Resveratrol was administered orally at the dose of 25 mg kg−1 body weight daily for three weeks to lean and obese mice. Resveratrol had no effect on body weight or blood glucose levels in obese mice. Lipid peroxides were significantly increased in brain of obese mice. The enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and nonenzymatic antioxidants tocopherol, ascorbic acid, and glutathione were decreased in obese mice brain. Administration of resveratrol decreased lipid peroxide levels and upregulated the antioxidant activities in obese mice brain. Our findings indicate a neuroprotective effect of resveratrol by preventing oxidative damage in brain tissue of obese mice. PMID:24163719

  3. CCK Response Deficiency in Synphilin-1 Transgenic Mice

    PubMed Central

    Smith, Wanli W.; Smith, Megan; Yang, Dejun; Choi, Pique P.; Moghadam, Alexander; Li, Tianxia; Moran, Timothy H.

    2015-01-01

    Previously, we have identified a novel role for the cytoplasmic protein, synphilin-1(SP1), in the controls of food intake and body weight in both mice and Drosophila. Ubiquitous overexpression of human SP1 in brain neurons in transgenic mice results in hyperphagia expressed as an increase in meal size. However, the mechanisms underlying this action of SP1 remain to be determined. Here we investigate a potential role for altered gut feedback signaling in the effects of SP1 on food intake. We examined responses to peripheral administration of cholecytokinin (CCK), amylin, and the glucagon like peptide-1 (GLP-1) receptor agonist, exendin-4. Intraperitoneal administration of CCK at doses ranging from 1–10 nmol/kg significantly reduced glucose intake in wild type (WT) mice, but failed to affect intake in SP1 transgenic mice. Moreover, there was a significant attenuation of CCK-induced c-Fos expression in the dorsal vagal complex in SP1 transgenic mice. In contrast, WT and SP1 transgenic mice were similarly responsive to both amylin and exendin-4 treatment. These studies demonstrate that SP1 results in a CCK response deficiency that may contribute to the increased meal size and overall hyperphagia in synphillin-1 transgenic mice. PMID:26569394

  4. Identification of a neurovascular signaling pathway regulating seizures in mice

    PubMed Central

    Fredriksson, Linda; Stevenson, Tamara K; Su, Enming J; Ragsdale, Margaret; Moore, Shannon; Craciun, Stefan; Schielke, Gerald P; Murphy, Geoffrey G; Lawrence, Daniel A

    2015-01-01

    Objective A growing body of evidence suggests that increased blood–brain barrier (BBB) permeability can contribute to the development of seizures. The protease tissue plasminogen activator (tPA) has been shown to promote BBB permeability and susceptibility to seizures. In this study, we examined the pathway regulated by tPA in seizures. Methods An experimental model of kainate-induced seizures was used in genetically modified mice, including mice deficient in tPA (tPA−/−), its inhibitor neuroserpin (Nsp−/−), or both (Nsp:tPA−/−), and in mice conditionally deficient in the platelet-derived growth factor receptor alpha (PDGFRα). Results Compared to wild-type (WT) mice, Nsp−/− mice have significantly reduced latency to seizure onset and generalization; whereas tPA−/− mice have the opposite phenotype, as do Nsp:tPA−/− mice. Furthermore, interventions that maintain BBB integrity delay seizure propagation, whereas osmotic disruption of the BBB in seizure-resistant tPA−/− mice dramatically reduces the time to seizure onset and accelerates seizure progression. The phenotypic differences in seizure progression between WT, tPA−/−, and Nsp−/− mice are also observed in electroencephalogram recordings in vivo, but absent in ex vivo electrophysiological recordings where regulation of the BBB is no longer necessary to maintain the extracellular environment. Finally, we demonstrate that these effects on seizure progression are mediated through signaling by PDGFRα on perivascular astrocytes. Interpretation Together, these data identify a specific molecular pathway involving tPA-mediated PDGFRα signaling in perivascular astrocytes that regulates seizure progression through control of the BBB. Inhibition of PDGFRα signaling and maintenance of BBB integrity might therefore offer a novel clinical approach for managing seizures. PMID:26273685

  5. State Machine Operation of the MICE Cooling Channel

    NASA Astrophysics Data System (ADS)

    Hanlet, Pierrick; Mice Collaboration

    2014-06-01

    The Muon Ionization Cooling Experiment (MICE) is a demonstration experiment to prove the feasibility of cooling a beam of muons for use in a Neutrino Factory and/or Muon Collider. The MICE cooling channel is a section of a modified Study II cooling channel which will provide a 10% reduction in beam emittance. In order to ensure a reliable measurement, MICE will measure the beam emittance before and after the cooling channel at the level of 1%, a relative measurement of 0.001. This renders MICE a precision experiment which requires strict controls and monitoring of all experimental parameters in order to control systematic errors. The MICE Controls and Monitoring system is based on EPICS and integrates with the DAQ, Data monitoring systems, and a configuration database. The cooling channel for MICE has between 12 and 18 superconductnig solenoid coils in 3 to 7 magnets, depending on the staged development of the experiment. The magnets are coaxial and in close proximity which requires coordinated operation of the magnets when ramping, responding to quench conditions, and quench recovery. To reliably manage the operation of the magnets, MICE is implementing state machines for each magnet and an over-arching state machine for the magnets integrated in the cooling channel. The state machine transitions and operating parameters are stored/restored to/from the configuration database and coupled with MICE Run Control. Proper implementation of the state machines will not only ensure safe operation of the magnets, but will help ensure reliable data quality. A description of MICE, details of the state machines, and lessons learned from use of the state machines in recent magnet training tests will be discussed.

  6. Facial expressions of mice in aggressive and fearful contexts.

    PubMed

    Defensor, Erwin B; Corley, Michael J; Blanchard, Robert J; Blanchard, D Caroline

    2012-12-01

    Some animals display a variety of context dependent facial expressions. Previous studies have shown that rodents display a facial grimace while in pain. To determine if the facial expressions of mice extend beyond pain, facial expressions were analyzed in the presence of non-social, social and predator stimuli. In a vibrissae contact test, the whiskers of mice were stroked by the bristles of a brush. In a social proximity test, two mice were placed together in a small chamber where contact was virtually unavoidable. In a resident-intruder test of aggression, an unknown mouse was placed into the homecage of another mouse. In a cat odor exposure test and in a live rat exposure test, mice were presented with the respective stimuli. Results from this study indicated that mice showed two patterns of expression, either a full display of changes in the measured facial components, characterized by tightened eyes, flattened ears, nose swells and cheek swells; or a more limited display of these facial changes. The full display of changes occurred in the vibrissae contact test, the social proximity test, and in resident mice in the resident-intruder test. The more limited display of facial changes occurred in the cat odor exposure test, the rat exposure test and in intruder mice in the resident-intruder test. The differential display of facial changes across conditions indicated that mice showed tightened eyes and flattened ears in situations that provided the immediate potential for contact, suggesting that such changes are involved in protection of sensitive and/or vulnerable body parts. Furthermore, the display of facial expressions by mice indicates that these expressions are widely distributed across evolution. PMID:22484562

  7. Identification of Hepatocarcinogen-Resistance Genes in Dba/2 Mice

    PubMed Central

    Lee, G. H.; Bennett, L. M.; Carabeo, R. A.; Drinkwater, N. R.

    1995-01-01

    Male DBA/2J mice are ~20-fold more susceptible than male C57BL/6J mice to hepatocarcinogenesis induced by perinatal treatment with N,N-diethylnitrosamine (DEN). In order to elucidate the genetic control of hepatocarcinogenesis in DBA/2J mice, male BXD recombinant inbred, D2B6F(1) X B6 backcross, and D2B6F(2) intercross mice were treated at 12 days of age with DEN and liver tumors were enumerated at 32 weeks. Interestingly, the distribution of mean tumor multiplicities among BXD recombinant inbred strains indicated that hepatocarcinogen-sensitive DBA/2 mice carry multiple genes with opposing effects on the susceptibility to liver tumor induction. By analyzing D2B6F(1) X B6 backcross and D2B6F(2) intercross mice for their liver tumor multiplicity phenotypes and for their genotypes at simple sequence repeat marker loci, we mapped two resistance genes carried by DBA/2J mice, designated Hcr1 and -2, to chromosomes 4 and 10, respectively. Hcr1 and Hcr2 resolved the genetic variance in the backcross population well, indicating that these resistance loci are the major determinants of the variance in the backcross population. Although our collection of 100 simple sequence repeat markers allowed linkage analysis for ~95% of the genome, we failed to map any sensitivity alleles for DBA/2J mice. Thus, it is likely that the susceptibility of DBA/2J mice is the consequence of the combined effects of multiple sensitivity loci. PMID:7705639

  8. Effect of iron on antibacterial immunity in vaccinated mice.

    PubMed

    Kochan, I; Wagner, S K; Wasynczuk, J

    1984-02-01

    The effect of iron on resistance to Salmonella typhimurium was investigated in mice inoculated with vaccines prepared from live and avirulent (SL3770) or killed and virulent (SR11 or LT2) bacteria. It has been found that mice vaccinated with SL3770 vaccine develop an immunity which can be neutralized with iron. Iron promoted the development of lethal infections by serving as a growth-essential nutrilite for infecting bacteria and by neutralizing the acquired immunity. The titration of this dual effect of iron showed that more iron was needed to neutralize the immunity in vaccinated animals than to promote bacterial growth in normal animals. In the presence of a sufficient amount of exogenous iron, as few as 10 bacteria caused lethal infections in normal and immune mice with the same effectiveness. This iron-sensitive immunity could be changed to iron-resistant immunity by the immunological stimulation of SL3770-vaccinated mice with a sonicated vaccine prepared from heat-killed SR11 or LT2 bacteria. In distinction to iron-sensitive immunity, iron-resistant immunity could be transferred from SR11- or LT2-stimulated to normal mice with serum. Although effective in the transfer of antibacterial immunity, sera of SR11- or LT2-stimulated mice supported the growth of virulent bacteria as well as did sera of normal mice. The absorption of immune serum with either SR11 or LT2 bacteria removed its protective quality, but the sensitized bacteria remained as infectious as untreated bacteria for iron-treated normal mice. Only in SL3770-vaccinated mice were the immune serum-sensitized bacteria not able to cause the infection in spite of daily treatment with iron. These results suggest that iron-resistant immunity is due to the synergistic action of specific antibody and phagocytes of immunologically stimulated animals. PMID:6363291

  9. Effect of iron on antibacterial immunity in vaccinated mice.

    PubMed Central

    Kochan, I; Wagner, S K; Wasynczuk, J

    1984-01-01

    The effect of iron on resistance to Salmonella typhimurium was investigated in mice inoculated with vaccines prepared from live and avirulent (SL3770) or killed and virulent (SR11 or LT2) bacteria. It has been found that mice vaccinated with SL3770 vaccine develop an immunity which can be neutralized with iron. Iron promoted the development of lethal infections by serving as a growth-essential nutrilite for infecting bacteria and by neutralizing the acquired immunity. The titration of this dual effect of iron showed that more iron was needed to neutralize the immunity in vaccinated animals than to promote bacterial growth in normal animals. In the presence of a sufficient amount of exogenous iron, as few as 10 bacteria caused lethal infections in normal and immune mice with the same effectiveness. This iron-sensitive immunity could be changed to iron-resistant immunity by the immunological stimulation of SL3770-vaccinated mice with a sonicated vaccine prepared from heat-killed SR11 or LT2 bacteria. In distinction to iron-sensitive immunity, iron-resistant immunity could be transferred from SR11- or LT2-stimulated to normal mice with serum. Although effective in the transfer of antibacterial immunity, sera of SR11- or LT2-stimulated mice supported the growth of virulent bacteria as well as did sera of normal mice. The absorption of immune serum with either SR11 or LT2 bacteria removed its protective quality, but the sensitized bacteria remained as infectious as untreated bacteria for iron-treated normal mice. Only in SL3770-vaccinated mice were the immune serum-sensitized bacteria not able to cause the infection in spite of daily treatment with iron. These results suggest that iron-resistant immunity is due to the synergistic action of specific antibody and phagocytes of immunologically stimulated animals. PMID:6363291

  10. Pulmonary effects of inhaled diesel exhaust in aged mice

    SciTech Connect

    Sunil, Vasanthi R.; Patel, Kinal J.; Mainelis, Gediminas; Turpin, Barbara J.; Ridgely, Sherritta; Laumbach, Robert J.; Kipen, Howard M.; Nazarenko, Yevgen; Veleeparambil, Manoj; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2009-12-15

    Pulmonary morbidity and mortality resulting from exposure to fine particulate matter (PM) increases with age. The present studies analyzed potential mechanisms underlying increased susceptibility of the elderly to PM using diesel exhaust (DE) as a model. Mice (2 m and 18 m) were exposed to DE (0, 300, and 1000 mug/m{sup 3}) for 3 h once (single) or 3 h/day for 3 days (repeated). Bronchoalveolar lavage fluid (BAL), serum and lung tissue were collected 0 and 24 h later. Exposure to DE resulted in structural alterations in the lungs of older but not younger mice, including patchy thickening of the alveolar septa and inflammatory cell localization in alveolar spaces. These effects were most pronounced 24 h after a single exposure to the higher dose of DE. Significant increases in BAL nitrogen oxides were also noted in older mice, as well as expression of lipocalin 24p3, an oxidative stress marker in the lung with no effects in younger mice. Following DE inhalation, expression of Tumor Necrosis Factor alpha (TNFalpha) was upregulated in lungs of both younger and older mice; however, this was attenuated in older animals. Whereas exposure to DE resulted in increases in lung Interleukin-6 (IL-6) expression in both older and younger mice, IL-8 increased only in older animals. In younger mice, constitutive expression of manganese superoxide dismutase (MnSOD) decreased after DE exposure, while in older mice, constitutive MnSOD was not detectable and DE had no effect on expression of this antioxidant. Taken together, these results suggest that altered generation of inflammatory mediators and MnSOD may contribute to increased susceptibility of older mice to inhaled DE.

  11. Taste sensitivities to PROP and PTC vary independently in mice.

    PubMed

    Nelson, Theodore M; Munger, Steven D; Boughter, John D

    2003-10-01

    Mammals use common mechanisms to detect, transduce and process taste stimulus information. For example, they share families of receptors that respond to amino acids, and sweet- and bitter-tasting stimuli. Nonetheless, it also clear that different species exhibit unique taste sensitivities that may reflect specific genetic variations. In humans, sensitivities to the chemically similar, bitter-tasting compounds 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC) are heritable and strongly correlated, suggesting a common genetic basis. However, it is unknown whether PROP and PTC taste sensitivities are similarly correlated in mice. Here we report that PROP and PTC taste sensitivities vary independently between two inbred strains of mice. In brief-access taste tests C3HeB/FeJ (C3) and SWR/J (SW) mice possess similar taste sensitivity to PTC, while SW mice are significantly more sensitive to PROP than are C3 mice. In two-bottle preference tests, however, SW mice display greater aversion to both compounds. This discrepancy may be explained by the observation that SW mice consumed taste solutions at a greater rate during the intake test than did C3 mice. Therefore, PTC avoidance is correlated with the amount of PTC consumed in the intake tests rather than the concentration of PTC tested. These findings suggest that post-ingestive factors play a significant role in PTC avoidance during intake tests and highlight an important advantage of brief-access tests over intake tests in resolving the gustatory and post-ingestive contributions to taste-related behaviors. Most strikingly, these results demonstrate that in mice, unlike in humans, PTC and PROP taste sensitivities vary independently, thereby suggesting a subtle functional diversity of bitter-taste mechanisms across mammalian species. PMID:14627538

  12. Impaired Bone Formation in Pdia3 Deficient Mice

    PubMed Central

    Wang, Yun; Nizkorodov, Alexandr; Riemenschneider, Kelsie; Lee, Christopher S. D.; Olivares-Navarrete, Rene; Schwartz, Zvi; Boyan, Barbara D.

    2014-01-01

    1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3) mediates 1α,25(OH)2D3 initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/− heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality. Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis of the tibias. In comparison to wild type mice, Pdia3 heterozygous mice displayed expanded growth plates associated with decreased tether formation. Histomorphometry also showed that the hypertrophic zone in Pdia3+/− mice was more cellular than seen in wild type growth plates. Metaphyseal trabecular bone in Pdia3+/− mice exhibited an age-dependent phenotype with lower BV/TV and trabecular numbers, which was most pronounced at 15 weeks of age. Bone marrow cells from Pdia3+/− mice exhibited impaired osteoblastic differentiation, based on reduced expression of osteoblast markers and mineral deposition compared to cells from wild type animals. Collectively, our findings provide in vivo evidence that PDIA3 is essential for normal skeletal development. The fact that the Pdia3+/− heterozygous mice share a similar growth plate and bone phenotype to nVdr knockout mice, suggests that PDIA3-mediated rapid membrane signaling might be an alternative mechanism responsible for 1α,25(OH)2D3’s actions in regulating skeletal development. PMID:25405762

  13. Altered anxiety and defensive behaviors in Bax knockout mice.

    PubMed

    Luedke, Angela C; Boucher, Pierre O; Niel, Lee; Holmes, Melissa M

    2013-02-15

    Developmental neuronal cell death is critically regulated by the pro-death protein Bax. Bax-/- mice exhibit increased neuron number, the elimination of several neural sex differences, and altered socio-sexual behaviors. Here we examined the effects of Bax gene deletion on anxiety and defensive behaviors by comparing the responses of male and female wildtype and Bax-/- mice to two different tests. On the elevated plus maze, Bax-/- mice of both sexes made more entries into and spent more time in the outer portion of open arms, indicating decreased anxiety compared to wildtype animals. Next, we exposed mice to two odors: trimethylthiazoline (TMT), an olfactory component of fox feces that rodents find aversive, and butyric acid (BA), an aversive odor without ecological significance. Each odor was presented individually and all animals were tested with both odors in a counterbalanced design. TMT was consistently more aversive than BA across a variety of behaviors (e.g., mice spent less time close to the odor source). Overall, Bax -/- mice showed fewer stretch approaches to both TMT and BA than wildtypes, but they avoided the odor source more (e.g., fewer contacts and less time spent in proximity). Finally, no effect of genotype was seen in baseline olfactory behavior; all mice were able to locate a buried food item, demonstrating that Bax-/- mice do not have impaired olfaction per se. Collectively, these data suggest a change in strategy with anxiety and defensive behaviors in Bax-/- mice, indicating that alterations in cell number affect more general mechanisms of fear and anxiety in addition to behaviors directly related to reproduction. PMID:23142367

  14. Striatal dopamine receptor plasticity in neurotensin deficient mice

    PubMed Central

    Chastain, Lucy G.; Qu, Hongyan; Bourke, Chase H.; Iuvone, P. Michael; Dobner, Paul R.; Nemeroff, Charles B.; Kinkead, Becky

    2015-01-01

    Schizophrenia is thought to be caused, at least in part, by dysfunction in striatal dopamine neurotransmission. Both clinical studies and animal research have implicated the dopamine neuromodulator neurotensin (NT) in the pathophysiology of schizophrenia. Utilizing male mice lacking the NT gene (NT?/?), these studies examined the consequences of NT deficiency on dopaminergic tone and function, investigating (1) dopamine concentrations and dopamine receptor and transporter expression and binding in dopaminergic terminal regions, and (2) the behavioral effects of selective dopamine receptor agonists on locomotion and sensorimotor gating in adult NT?/? mice compared to wildtype (NT+/+) mice. NT?/? mice did not differ from NT+/+ mice in concentrations of dopamine or its metabolite DOPAC in any brain region examined. However, NT?/? mice showed significantly increased D1 receptor, D2 receptor, and dopamine transporter (DAT) mRNA in the caudate putamen compared to NT+/+ controls. NT?/? mice also showed elevated D2 receptor binding densities in both the caudate putamen and nucleus accumbens shell compared to NT+/+ mice. In addition, some of the behavioral effects of the D1-type receptor agonist SKF-82958 and the D2-type receptor agonist quinpirole on locomotion, startle amplitude, and prepulse inhibition were dose-dependently altered in NT?/? mice, showing altered D1-type and D2-type receptor sensitivity to stimulation by agonists in the absence of NT. The results indicate that NT deficiency alters striatal dopamine receptor expression, binding, and function. This suggests a critical role for the NT system in the maintenance of striatal DA system homeostasis and implicates NT deficiency in the etiology of dopamine-associated disorders such as schizophrenia. PMID:25449842

  15. Postpartum estrogen withdrawal impairs hippocampal neurogenesis and causes depression- and anxiety-like behaviors in mice.

    PubMed

    Zhang, Zhuan; Hong, Juan; Zhang, Suyun; Zhang, Tingting; Sha, Sha; Yang, Rong; Qian, Yanning; Chen, Ling

    2016-04-01

    Postpartum estrogen withdrawal is known to be a particularly vulnerable time for depressive symptoms. Ovariectomized adult mice (OVX-mice) treated with hormone-simulated pregnancy (HSP mice) followed by a subsequent estradiol benzoate (EB) withdrawal (EW mice) exhibited depression- and anxiety-like behaviors, as assessed by forced swim, tail suspension and elevated plus-maze, while HSP mice, OVX mice or EB-treated OVX mice (OVX/EB mice) did not. The survival and neurite growth of newborn neurons in hippocampal dentate gyrus were examined on day 5 after EW. Compared with controls, the numbers of 28-day-old BrdU(+) and BrdU(+)/NeuN(+) cells were increased in HSP mice but significantly decreased in EW mice; the numbers of 10-day-old BrdU(+) cells were increased in HSP mice and OVX/EB mice; and the density of DCX(+) fibers was reduced in EW mice and OVX mice. The phosphorylation of hippocampal NMDA receptor (NMDAr) NR2B subunit or Src was increased in HSP mice but decreased in EW mice. NMDAr agonist NMDA prevented the loss of 28-day-old BrdU(+) cells and the depression- and anxiety-like behaviors in EW mice. NR2B inhibitor Ro25-6981 or Src inhibitor dasatinib caused depression- and anxiety-like behaviors in HSP mice with the reduction of 28-day-old BrdU(+) cells. The hippocampal BDNF levels were reduced in EW mice and OVX mice. TrkB receptor inhibitor K252a reduced the density of DCX(+) fibers in HSP mice without the reduction of 28-day-old BrdU(+) cells, or the production of affective disorder. Collectively, these results indicate that postpartum estrogen withdrawal impairs hippocampal neurogenesis in mice that show depression- and anxiety-like behaviors. PMID:26803529

  16. Hepatic steatosis in transgenic mice overexpressing human histone deacetylase 1

    SciTech Connect

    Wang, Ai-Guo; Seo, Sang-Beom; Moon, Hyung-Bae; Shin, Hye-Jun; Kim, Dong Hoon; Kim, Jin-Man; Lee, Tae-Hoon; Kwon, Ho Jeong; Yu, Dae-Yeul . E-mail: dyyu10@kribb.re.kr; Lee, Dong-Seok . E-mail: lee10@kribb.re.kr

    2005-05-06

    It is generally thought that histone deacetylases (HDACs) play important roles in the transcriptional regulation of genes. However, little information is available concerning the specific functions of individual HDACs in disease states. In this study, two transgenic mice lines were established which harbored the human HDAC1 gene. Overexpressed HDAC1 was detected in the nuclei of transgenic liver cells, and HDAC1 enzymatic activity was significantly higher in the transgenic mice than in control littermates. The HDAC1 transgenic mice exhibited a high incidence of hepatic steatosis and nuclear pleomorphism. Molecular studies showed that HDAC1 may contribute to nuclear pleomorphism through the p53/p21 signaling pathway.

  17. Incidence of plutonium-induced bone cancer in neutered mice

    SciTech Connect

    Taylor, G.N.; Gardner, P.; Mays, C.W.; Wrenn, M.E.; Charrier, K.

    1981-03-01

    The incidence of bone cancer, after a single i.p. injection of monomeric /sup 239/Pu citrate, is significantly higher in female than in male mice. To evaluate the role of the gonads in this sex-related difference, male and female C57BL/Do (albino) mice were castrated at 40 days of age. Fifty days later, they were given injections of /sup 239/Pu. After castration, the frequency of bone sarcomas in the two sexes was approximately equal. This resulted from an increased incidence in the castrated males and a decreased incidence in the ovariectomized females as compared to the intact plutonium-treated mice.

  18. Attenuation of oscillatory potentials in nob2 mice

    PubMed Central

    Peachey, Neal S.

    2010-01-01

    Purpose To examine changes in inner retinal function of nob2 mice, expressing a null mutation in Cacna1f encoding the CaV1.4 subunit of voltage-dependent calcium channels. CACNA1F mutations underlie one form of incomplete X-linked congenital stationary night blindness (CSNB2). In addition to a loss of dark-adapted (rod-driven) visual sensitivity, electroretinogram (ERG) b-waves and oscillatory potentials (OPs) are decreased in CSNB2 patients. Methods ERGs were recorded under dark-and light-adapted conditions from the corneal surface of nob2 mice, WT littermates and nob4 mice. ERG frequency spectra were calculated by fast Fourier transform (FFT). A FFT-based high-pass filter was used to derive OP waveforms. Results Under dark-adapted conditions, the dominant frequency of the OPs varied between 90 to 120 Hz in WT mice. In WT mice, OP frequency first increased with flash intensity and then decreased at the highest flash levels while overall OP amplitude increased monotonically with increasing flash intensity. In response to low stimulus flashes, reliable OPs were not obtained from nob2 mice. OPs were only seen at stimulus intensities at or above −1.8 log cd s/m2, where they occurred at a lower frequency range (70–90 Hz) than for WT mice. When flash stimuli were superimposed against a steady rod-desensitizing adapting field, the amplitude and frequency of WT OPs increased with flash intensity above 0.4 log cd s/m2. In comparison to WT results, cone-mediated OPs obtained from nob2 mice were smaller in amplitude, of lower frequency and had delayed implicit times. We compared the extent to which OPs and the b-wave were reduced in nob2 mice, by normalizing to the results obtained from WT mice. In comparison to the b-wave, the OPs were relatively spared, under both dark- and light-adapted conditions. Conclusions In nob2 mice, rod- and cone-driven OPs are reduced in amplitude and occur at a lower frequency range. Since CaV1.4 is expressed in both the inner and outer plexiform layers, these changes are likely to reflect reduced transmission from photoreceptors to bipolar cells as well as alterations in inner retinal function. That the OPs were better preserved than b-waves suggests that inner retinal pathways may be reorganized in response to the decreased bipolar cell response in nob2 mice. PMID:17479213

  19. The design, construction and performance of the MICE target

    NASA Astrophysics Data System (ADS)

    Booth, C. N.; Hodgson, P.; Howlett, L.; Nicholson, R.; Overton, E.; Robinson, M.; Smith, P. J.; Apollonio, M.; Barber, G.; Dobbs, A.; Leaver, J.; Long, K. R.; Shepherd, B.; Adams, D.; Capocci, E.; McCarron, E.; Tarrant, J.

    2013-03-01

    The pion-production target that serves the MICE Muon Beam consists of a titanium cylinder that is dipped into the halo of the ISIS proton beam. The design and construction of the MICE target system are described along with the quality-assurance procedures, electromagnetic drive and control systems, the readout electronics, and the data-acquisition system. The performance of the target is presented together with the particle rates delivered to the MICE Muon Beam. Finally, the beam loss in ISIS generated by the operation of the target is evaluated as a function of the particle rate, and the operating parameters of the target are derived.

  20. The Results of Recent MICE Superconducting Spectrometer Solenoid Test

    SciTech Connect

    Green, Michael A; Virostek, Steve P.; Zisman, Michael S.

    2010-10-15

    The MICE spectrometer solenoid magnets will be the first magnets to be installed within the MICE cooling channel. The MICE spectrometer solenoids may be the largest magnets that have been cooled using small two stage coolers. During the previous test of this magnet, the cooler first stage temperatures were too high. The causes of some of the extra first stage heat load has been identified and corrected. The rebuilt magnet had a single stage GM cooler in addition to the three pulse tube coolers. The added cooler reduces the temperature of the top of the HTS leads, the shield and of the first stage of the pulse tube coolers.

  1. Social modulation of pain as evidence for empathy in mice.

    PubMed

    Langford, Dale J; Crager, Sara E; Shehzad, Zarrar; Smith, Shad B; Sotocinal, Susana G; Levenstadt, Jeremy S; Chanda, Mona Lisa; Levitin, Daniel J; Mogil, Jeffrey S

    2006-06-30

    Empathy is thought to be unique to higher primates, possibly to humans alone. We report the modulation of pain sensitivity in mice produced solely by exposure to their cagemates, but not to strangers, in pain. Mice tested in dyads and given an identical noxious stimulus displayed increased pain behaviors with statistically greater co-occurrence, effects dependent on visual observation. When familiar mice were given noxious stimuli of different intensities, their pain behavior was influenced by their neighbor's status bidirectionally. Finally, observation of a cagemate in pain altered pain sensitivity of an entirely different modality, suggesting that nociceptive mechanisms in general are sensitized. PMID:16809545

  2. Serospecific protection of mice against intranasal infection with Bordetella pertussis.

    PubMed

    Robinson, A; Gorringe, A R; Funnell, S G; Fernandez, M

    1989-08-01

    The ability of purified serospecific agglutinogens from Bordetella pertussis to protect mice against intranasal infection has been examined. Immunization with agglutinogen 2 protected mice against infection with 1.2.0 or 1.2.3 serotypes of B. pertussis, whereas immunization with agglutinogen 3 protected mice against infection with all serotypes. More importantly immunization with serospecific agglutinogen resulted in immune selection so that organisms recovered following infection did not express the immunizing antigen. The results are consistent with the suggestions that protection of children with whole cell pertussis vaccine is to some extent serospecific and that agglutinogens should be considered as constituents of acellular pertussis vaccines. PMID:2573215

  3. Innate resistance of mice to Salmonella typhi infection.

    PubMed Central

    O'Brien, A D

    1982-01-01

    The basis for the natural resistance of mice to Salmonella typhi was examined. In contrast to Salmonella typhimurium, the virulence of S. typhi for mice was independent of the mouse strain and was not affected by inactivation of murine macrophages with silica. However, mice were more susceptible to S. typhi when given iron alone or iron and an iron chelator. The results suggest that the failure of S. typhi to undergo net growth in murine tissues reflects an inability of the bacterium to multiply rather than rapid killing by resident macrophages. PMID:7152679

  4. Humanized mice for immune system investigation: progress, promise and challenges

    PubMed Central

    Shultz, Leonard D.; Brehm, Michael A.; Garcia, J. Victor; Greiner, Dale L.

    2013-01-01

    Preface Significant advances in our understanding of the in vivo functions of human cells, tissues and immune systems have resulted from the development of mouse strains that are based on severely immunodeficient mice expressing mutations in the interleukin-2 (IL-2) receptor common γ-chain locus. These mouse strains support the engraftment of a functional human immune system and permit detailed analysis of human immune biology, development and functions. In this Review, we discuss recent advances in the development of humanized mice, the lessons learned, the remaining challenges and the promise of using humanized mice for the in vivo study of human immunology. PMID:23059428

  5. IL-4 Deficiency Is Associated with Mechanical Hypersensitivity in Mice

    PubMed Central

    Üçeyler, Nurcan; Topuzoğlu, Tengü; Schießer, Peter; Hahnenkamp, Saskia; Sommer, Claudia

    2011-01-01

    Interleukin-4 (IL-4) is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko) mice to characterize their pain behavior before and after chronic constriction injury (CCI) of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS) of IL-4 ko mice in comparison with wildtype (wt) mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001), while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF), IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001) 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014). Remarkably, CCI induced TNF (p<0.01), IL-1β (p<0.05), IL-10 (p<0.05), and IL-13 (p<0.001) gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion. PMID:22164245

  6. The acyl-CoA binding protein is required for normal epidermal barrier function in mice[S

    PubMed Central

    Bloksgaard, Maria; Bek, Signe; Marcher, Ann-Britt; Neess, Ditte; Brewer, Jonathan; Hannibal-Bach, Hans Kristian; Helledie, Torben; Fenger, Christina; Due, Marianne; Berzina, Zane; Neubert, Reinhard; Chemnitz, John; Finsen, Bente; Clemmensen, Anders; Wilbertz, Johannes; Saxtorph, Henrik; Knudsen, Jens; Bagatolli, Luis; Mandrup, Susanne

    2012-01-01

    The acyl-CoA binding protein (ACBP) is a 10 kDa intracellular protein expressed in all eukaryotic species. Mice with targeted disruption of Acbp (ACBP?/? mice) are viable and fertile but present a visible skin and fur phenotype characterized by greasy fur and development of alopecia and scaling with age. Morphology and development of skin and appendages are normal in ACBP?/? mice; however, the stratum corneum display altered biophysical properties with reduced proton activity and decreased water content. Mass spectrometry analyses of lipids from epidermis and stratum corneum of ACBP+/+ and ACBP?/? mice showed very similar composition, except for a significant and specific decrease in the very long chain free fatty acids (VLC-FFA) in stratum corneum of ACBP?/? mice. This finding indicates that ACBP is critically involved in the processes that lead to production of stratum corneum VLC-FFAs via complex phospholipids in the lamellar bodies. Importantly, we show that ACBP?/? mice display a ?50% increased transepidermal water loss compared with ACBP+/+ mice. Furthermore, skin and fur sebum monoalkyl diacylglycerol (MADAG) levels are significantly increased, suggesting that ACBP limits MADAG synthesis in sebaceous glands. In summary, our study shows that ACBP is required for production of VLC-FFA for stratum corneum and for maintaining normal epidermal barrier function. PMID:22829653

  7. Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain.

    PubMed

    Bissa, Massimiliano; Pacchioni, Sole Maria; Zanotto, Carlo; De Giuli Morghen, Carlo; Illiano, Elena; Granucci, Francesca; Zanoni, Ivan; Broggi, Achille; Radaelli, Antonia

    2013-12-26

    The first-generation smallpox vaccine was based on live vaccinia virus (VV) and it successfully eradicated the disease worldwide. Therefore, it was not administered any more after 1980, as smallpox no longer existed as a natural infection. However, emerging threats by terrorist organisations has prompted new programmes for second-generation vaccine development based on attenuated VV strains, which have been shown to cause rare but serious adverse events in immunocompromised patients. Considering the closely related animal poxviruses that might also be used as bioweapons, and the increasing number of unvaccinated young people and AIDS-affected immunocompromised subjects, a safer and more effective smallpox vaccine is still required. New avipoxvirus-based vectors should improve the safety of conventional vaccines, and protect from newly emerging zoonotic orthopoxvirus diseases and from the threat of deliberate release of variola or monkeypox virus in a bioterrorist attack. In this study, DNA and fowlpox recombinants expressing the L1R, A27L, A33R and B5R genes were constructed and evaluated in a pre-clinical trial in mouse, following six prime/boost immunisation regimens, to compare their immunogenicity and protective efficacy against a challenge with the lethal VV IHD-J strain. Although higher numbers of VV-specific IFN?-producing T lymphocytes were observed in the protected mice, the cytotoxic T-lymphocyte response and the presence of neutralising antibodies did not always correlate with protection. In spite of previous successful results in mice, rabbits and monkeys, where SIV/HIV transgenes were expressed by the fowlpox vector, the immune response elicited by these recombinants was low, and most of the mice were not protected. PMID:24050999

  8. CD8+ T-cell epitope mapping for pneumonia virus of mice in H-2b mice.

    PubMed

    Walsh, Kevin B; Sidney, John; Welch, Megan; Fremgen, Daniel M; Sette, Alessandro; Oldstone, Michael B A

    2013-09-01

    The paramyxovirus pneumonia virus of mice (PVM) is a rodent model of human respiratory syncytial virus (hRSV) pathogenesis. Here we characterized the PVM-specific CD8(+) T-cell repertoire in susceptible C57BL/6 mice. In total, 15 PVM-specific CD8(+) T-cell epitopes restricted by H-2D(b) and/or H-2K(b) were identified. These data open the door for using widely profiled, genetically manipulated C57BL/6 mice to study the contribution of epitope-specific CD8(+) T cells to PVM pathogenesis. PMID:23824814

  9. Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice

    PubMed Central

    Tateno, Chise; Kawase, Yosuke; Tobita, Yoshimi; Hamamura, Satoko; Ohshita, Hiroki; Yokomichi, Hiroshi; Sanada, Harumi; Kakuni, Masakazu; Shiota, Akira; Kojima, Yuha; Ishida, Yuji; Shitara, Hiroshi; Wada, Naoko A.; Tateishi, Hiromi; Sudoh, Masayuki; Nagatsuka, Shin-ichiro; Jishage, Kou-ichi; Kohara, Michinori

    2015-01-01

    We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID) mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps) replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID). We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expressionnot detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb) levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and useful hosts for producing chimeric mice for use in future long-term studies, including hepatitis virus infection analysis or drug toxicity studies. PMID:26536627

  10. Effects of Sleep Deprivation and Aging on Long-Term and Remote Memory in Mice

    ERIC Educational Resources Information Center

    Vecsey, Christopher G.; Park, Alan J.; Khatib, Nora; Abel, Ted

    2015-01-01

    Sleep deprivation (SD) following hippocampus-dependent learning in young mice impairs memory when tested the following day. Here, we examined the effects of SD on remote memory in both young and aged mice. In young mice, we found that memory is still impaired 1 mo after training. SD also impaired memory in aged mice 1 d after training, but, by a…

  11. CD34 EXPRESSION BY HAIR FOLLICLE STEM CELLS IS REQUIRED FOR SKIN TUMOR DEVELOPMENT IN MICE

    EPA Science Inventory

    We used knockout mice to show that a cell surface protein called CD34 is required for skin tumor formation in mice. Wild type mice treated with 7-12-Dimethylbenz(a)anthracene (DMBA) and a tumor promoter developed papillomas. When we treated CD34 knockout (KO) mice the same way, n...

  12. Myostatin null mice respond differently to dietary-induced and genetic obesity.

    PubMed

    Dilger, Anna C; Spurlock, Michael E; Grant, Alan L; Gerrard, David E

    2010-10-01

    Our objective was to determine sensitivity of myostatin null (MN) mice to obesity induction by dietary or genetic means. To induce dietary obesity, 3-week-old wild type (WT) and MN mice were fed diets with 60% calories (HF) or 10% calories from fat (LF) for 4 weeks. MN mice did gain body fat on the HF diet but to a lesser extent than WT mice. Body weight and fat content was similar in MN mice fed HF and LF diets. To induce genetic obesity, the MN mutation was incorporated into leptin db/db (DB) mice generating mice homozygous for each mutation (MNDB). Nine-week-old MNDB mice were obese, similar to DB mice. Body weight, body fat content, fat pad weight and adipocyte size were all increased in MNDB mice compared to MN and WT mice and were quite similar to DB mice. However, fasting blood glucose, an indicator of insulin resistance and diabetes, was reduced in MNDB mice compared to DB mice. These results indicate that MN mice gain less body fat than WT on a HF diet, but the MN mutation does not alter fat accumulation caused by DB mutation. Thus, MN mice are not always resistant to obesity development. PMID:20887312

  13. Effects of Sleep Deprivation and Aging on Long-Term and Remote Memory in Mice

    ERIC Educational Resources Information Center

    Vecsey, Christopher G.; Park, Alan J.; Khatib, Nora; Abel, Ted

    2015-01-01

    Sleep deprivation (SD) following hippocampus-dependent learning in young mice impairs memory when tested the following day. Here, we examined the effects of SD on remote memory in both young and aged mice. In young mice, we found that memory is still impaired 1 mo after training. SD also impaired memory in aged mice 1 d after training, but, by a

  14. Social factors modulate restraint stress induced hyperthermia in mice.

    PubMed

    Watanabe, Shigeru

    2015-10-22

    Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. PMID:26232073

  15. Hypoglycemic Effects of Glycosaminoglycan from Urechis unicinctus in Diabetic Mice

    PubMed Central

    Liu, Ping; Han, Xu; Cui, Qingman

    2015-01-01

    Abstract To further utilize glycosaminoglycan from Urechis unicinctus, the hypoglycemic effect and possible mechanism of glycosaminoglycan on diabetic mice were evaluated. Diabetes was induced in mice by intraperitoneal injections of streptozotocin for 3 consecutive days and fed with high-sugar and high-lipid fodder. After diabetes was confirmed, the hypoglycemic effect of glycosaminoglycan from U. unicinctus was investigated in the diabetic mice. Results demonstrated that glycosaminoglycan could significantly decrease blood glucose concentrations, HOMA-IR, AUG, and liver MDA content in diabetic mice. In addition, it significantly enhanced liver SOD and GSH-Px activity, as well as liver GCK activity and hepatic glycogen levels. Glycosaminoglycan from U. unicinctus exhibited efficacy against diabetes, suggesting its potential use as a natural intervention against diabetes. PMID:25289478

  16. Montelukast reduces seizures in pentylenetetrazol-kindled mice.

    PubMed

    Fleck, J; Temp, F R; Marafiga, J R; Jesse, A C; Milanesi, L H; Rambo, L M; Mello, C F

    2016-01-01

    Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research. PMID:26909785

  17. Endotracheal Intubation in Mice via Direct Laryngoscopy Using an Otoscope

    PubMed Central

    Thomas, Joanna L.; Dumouchel, Justin; Li, Jinghong; Magat, Jenna; Balitzer, Dana; Bigby, Timothy D.

    2014-01-01

    Mice, both wildtype and transgenic, are the principal mammalian model in biomedical research currently. Intubation and mechanical ventilation are necessary for whole animal experiments that require surgery under deep anesthesia or measurements of lung function. Tracheostomy has been the standard for intubating the airway in these mice to allow mechanical ventilation. Orotracheal intubation has been reported but has not been successfully used in many studies because of the substantial technical difficulty or a requirement for highly specialized and expensive equipment. Here we report a technique of direct laryngoscopy using an otoscope fitted with a 2.0 mm speculum and using a 20 G intravenous catheter as an endotracheal tube. We have used this technique extensively and reliably to intubate and conduct accurate assessments of lung function in mice. This technique has proven safe, with essentially no animal loss in experienced hands. Moreover, this technique can be used for repeated studies of mice in chronic models. PMID:24747695

  18. ?-Carotene ameliorates arsenic-induced toxicity in albino mice.

    PubMed

    Das, Ruma; Das, Avratanu; Roy, Amrita; Kumari, Uma; Bhattacharya, Sanjib; Haldar, Pallab Kanti

    2015-04-01

    The present study evaluated the ameliorative potential of ?-carotene (BCT) against experimentally induced arsenic toxicity in Swiss albino mice. BCT (5 and 10 mg/kg) was administered orally to mice 30 min before oral administration of arsenic trioxide (3 mg/kg) for 14 consecutive days. On 15th day, the body weights, organ weights, hematological profiles, serum biochemical profile; hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase; and DNA fragmentation were evaluated. Co-treatment with BCT markedly and significantly normalized body weights, organ weights, hematological profiles, serum biochemical profile and significantly modulated all the hepatic and renal biochemical parameters and DNA fragmentation in arsenic-intoxicated mice. The present findings conclude that ?-carotene possessed remarkable ameliorative effect against arsenic-induced toxicity in albino mice mediated by its antioxidant and antigenotoxic properties. PMID:25542264

  19. In Mice, Scientists Turn Stem Cells into Sperm

    MedlinePlus

    ... news/fullstory_157465.html In Mice, Scientists Turn Stem Cells Into Sperm Researchers from China say lab tests ... News) -- Scientists in China say they used mouse stem cells to create functional mouse sperm in the laboratory. ...

  20. Personalized chemotherapy profiling using cancer cell lines from selectable mice

    PubMed Central

    Kamiyama, Hirohiko; Rauenzahn, Sherri; Shim, Joong Sup; Karikari, Collins A.; Feldmann, Georg; Hua, Li; Kamiyama, Mihoko; Schuler, F. William; Lin, Ming-Tseh; Beaty, Robert M.; Karanam, Balasubramanyam; Liang, Hong; Mullendore, Michael E.; Mo, Guanglan; Hidalgo, Manuel; Jaffee, Elizabeth; Hruban, Ralph H.; Jinnah, H. A.; Roden, Richard B. S.; Jimeno, Antonio; Liu, Jun O.; Maitra, Anirban; Eshleman, James R.

    2013-01-01

    Purpose High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult, because contaminating stromal cells overgrow the malignant cells. Experimental Design We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts. Results Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. We screened one cell line with a 3,131-drug panel and identified seventy-seven FDA approved drugs with activity, including two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs. Conclusion Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice. PMID:23340293

  1. Thyroid function in mice with experimental autoimmune thyroiditis.

    PubMed Central

    Vladutiu, A O; Kenney, E M

    1985-01-01

    Mice of strains high and low responders to thyroglobulin were immunized with mouse thyroglobulin emulsified in Freund's complete adjuvant. Groups of mice were killed at weekly intervals and the serum thyroxine concentration was measured with a solid-phase RIA while the titre of thyroglobulin antibodies was determined by passive haemagglutination and the magnitude of thyroid infiltration with mononuclear cells was scored. In other groups of mice, similarly immunized, radioactive iodine uptake was measured at various times after immunization. In almost all mice the lowest level of thyroxine and the lowest radioiodine uptake were observed 2 weeks after immunization. There was no clear relationship between the thyroid function and the titre of thyroglobulin antibodies or the extent of the cellular infiltrates in the thyroid. PMID:4042424

  2. Status of MICE, the international Muon Ionization Cooling Experiment

    NASA Astrophysics Data System (ADS)

    Bross, Alan D.; MICE Collaboration

    2012-08-01

    The Muon Ionization Cooling Experiment (MICE) will demonstrate transverse muon ionization cooling and is thus a strategic R&D project for future muon facilities. It is under development at the Rutherford Appleton Laboratory in the United Kingdom.

  3. Human erythropoietin induces lung failure and erythrocytosis in transgenic mice.

    PubMed

    Kim, Myoung Ok; Kim, Sung Hyun; Shin, Mi Jung; Lee, Dong Beom; Kim, Tae Won; Kim, Kil Soo; Ha, Ji Hong; Lee, Sanggyu; Park, Yong Bok; Kim, Sun Jung; Ryoo, Zae Young

    2007-02-28

    We have expressed human erythropoietin (EPO) in transgenic mice using a recombinant EPO cDNA combined with a partial TPO construct. The gene was microinjected using standard techniques and five mice were detected as transgenic by PCR and further used as founders. The life span of the transgenic founders was much shorter than that of their normal littermates. Most of the tissues of the transgenic founders contained human EPO transcripts as judged by RT-PCR. Especially high expression levels were seen in the liver and lung. EPO protein levels in serum were examined by ELISA and ranged from 266, 414 mIU/ml. The number of red blood cell, white blood cell and hemoglobin in the hEPO transgenic mice was higher than in normal mice. These results indicate that overexpression of hEPO is deleterious and can provoke lung failure and erythrocytosis. PMID:17464207

  4. Montelukast reduces seizures in pentylenetetrazol-kindled mice

    PubMed Central

    Fleck, J.; Temp, F.R.; Marafiga, J.R.; Jesse, A.C.; Milanesi, L.H.; Rambo, L.M.; Mello, C.F.

    2016-01-01

    Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research. PMID:26909785

  5. Increased Anxiety in Offspring Reared by Circadian Clock Mutant Mice

    PubMed Central

    Koizumi, Hiroko; Kurabayashi, Nobuhiro; Watanabe, Yuto; Sanada, Kamon

    2013-01-01

    The maternal care that offspring receive from their mothers early in life influences the offspring’s development of emotional behavior in adulthood. Here we found that offspring reared by circadian clock-impaired mice show elevated anxiety-related behavior. Clock mutant mice harboring a mutation in Clock, a key component of the molecular circadian clock, display altered daily patterns of nursing behavior that is fragmented during the light period, instead of long bouts of nursing behavior in wild-type mice. Adult wild-type offspring fostered by Clock mutant mice exhibit increased anxiety-related behavior. This is coupled with reduced levels of brain serotonin at postnatal day 14, whose homeostasis during the early postnatal period is critical for normal emotional behavior in adulthood. Together, disruption of the circadian clock in mothers has an adverse impact on establishing normal anxiety levels in offspring, which may increase their risk of developing anxiety disorders. PMID:23776596

  6. Nod2 Mediates Susceptibility to Yersinia pseudotuberculosis in Mice

    PubMed Central

    Meinzer, Ulrich; Esmiol-Welterlin, Sophie; Barreau, Frederick; Berrebi, Dominique; Dussaillant, Monique; Bonacorsi, Stephane; Chareyre, Fabrice; Niwa-Kawakita, Michiko; Alberti, Corinne; Sterkers, Ghislaine; Villard, Claude; Lesuffleur, Thecla; Peuchmaur, Michel; Karin, Michael; Eckmann, Lars; Giovannini, Marco; Ollendorff, Vincent; Wolf-Watz, Hans; Hugot, Jean-Pierre

    2008-01-01

    Nucleotide oligomerisation domain 2 (NOD2) is a component of the innate immunity known to be involved in the homeostasis of Peyer patches (PPs) in mice. However, little is known about its role during gut infection in vivo. Yersinia pseudotuberculosis is an enteropathogen causing gastroenteritis, adenolymphitis and septicaemia which is able to invade its host through PPs. We investigated the role of Nod2 during Y. pseudotuberculosis infection. Death was delayed in Nod2 deleted and Crohn's disease associated Nod2 mutated mice orogastrically inoculated with Y. pseudotuberculosis. In PPs, the local immune response was characterized by a higher KC level and a more intense infiltration by neutrophils and macrophages. The apoptotic and bacterial cell counts were decreased. Finally, Nod2 deleted mice had a lower systemic bacterial dissemination and less damage of the haematopoeitic organs. This resistance phenotype was lost in case of intraperitoneal infection. We concluded that Nod2 contributes to the susceptibility to Y. pseudotuberculosis in mice. PMID:18648508

  7. DEVELOPMENTAL TOXICOGENOMIC STUDIES OF PFOA AND PFOS IN MICE.

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are developmentally toxic in rodents. To better understand the mechanism(s) associated with this toxicity, we have conducted transcript profiling in mice. In an initial study, pregnant animals were dosed througho...

  8. Rhabdomyosarcomas in Aging A/J Mice

    PubMed Central

    Sher, Roger B.; Cox, Gregory A.; Mills, Kevin D.; Sundberg, John P.

    2011-01-01

    Rhabdomyosarcomas (RSCs) are skeletal muscle neoplasms found in humans and domestic mammals. The A/J inbred strain developed a high frequency (between 70–80%) of adult pleomorphic type (APT) RSC at >20 months of age while BALB/cByJ also develop RSC but less frequently. These neoplasms invaded skeletal muscle surrounding either the axial or proximal appendicular skeleton and were characterized by pleomorphic cells with abundant eosinophilic cytoplasm, multiple nuclei, and cross striations. The diagnosis was confirmed by detection of alpha-sarcomeric actin and myogenin in the neoplastic cells using immunocytochemistry. The A/J strain, but not the related BALB/c substrains, is also characterised by a progressive muscular dystrophy homologous to limb-girdle muscular dystrophy type 2B. The association between the development of RSC in similar muscle groups to those most severely affected by the progressive muscular dystrophy suggested that these neoplasms developed from abnormal regeneration of the skeletal muscle exacerbated by the dysferlin mutation. Transcriptome analyses of RSCs revealed marked downregulation of genes in muscular development and function signaling networks. Non-synonymous coding SNPs were found in Myl1, Abra, Sgca, Ttn, and Kcnj12 suggesting these may be important in the pathogenesis of RSC. These studies suggest that A strains of mice can be useful models for dissecting the molecular genetic basis for development, progression, and ultimately for testing novel anticancer therapeutic agents dealing with rhabdomyosarcoma. PMID:21853140

  9. Exploratory behavior models of anxiety in mice.

    PubMed

    Crawley, J N

    1985-01-01

    Parameters of exploratory behaviors responsive to anti-anxiety drugs are reviewed with respect to their sensitivity and specificity for anxiolytics in mice. Mouse models appear to rest on a disinhibition of natural exploratory tendencies by anxiolytic treatments. Analysis of agonists of the brain benzodiazepine binding site, such as chlordiazepoxide and diazepam, significantly increase exploration of a hole-board, of a two-chambered light in equilibrium dark apparatus, increase social interaction under high levels of illumination, increase consumption of a novel food in an unfamiliar environment, and increase punished crossings in a footshock conflict paradigm. These tests detect anxiolytic responses at doses of benzodiazepines well within the clinically effective range. Pharmacological specificity was established for the hole-board and light in equilibrium transition tests, showing that non-anxiolytic categories of psychoactive drugs did not produce false positives. Open field behaviors and isolation-induced aggression were reduced by anxiolytics, at doses which may be within the sedative-hypnotic range. Analysis of antagonists of the brain benzodiazepine binding site did not show active antagonist properties in the light in equilibrium transitions model, although the antagonist Ro-15-1788 appeared to have partial agonist properties in the open field test, suggesting that rat models may be more sensitive to anxiogenic compounds than are mouse models. The wide separation between anxiolytic and sedative doses in mouse models recommend these exploration paradigms as good predictive screens for the testing of novel anxiolytic compounds. PMID:2858080

  10. Chemical induction of sperm abnormalities in mice.

    PubMed Central

    Wyrobek, A J; Bruce, W R

    1975-01-01

    The sperm of (C57BL X C3H)F1 mice were examined 1, 4, and 10 weeks after a subacute treatment with one of 25 chemicals at two or more dose levels. The fraction of sperm that were abnormal in shape was elevated above control values of 1.2-3.4% for methyl methanesulfonate, ethyl methanesulfonate, griseofulvin, benzo[a]pyrene, METEPA [tris(2-methyl-l-aziridinyl)phosphine oxide], THIO-TEPA [tris(l-aziridinyl)phosphine sulfide], mitomycin C, myleran, vinblastine sulphate, hydroxyurea, 3-methylcholanthrene, colchicine, actinomycin D, imuran, cyclophosphamide, 5-iododeoxyuridine, dichlorvos, aminopterin, and trimethylphosphate. Dimethylnitrosamine, urethane, DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane], 1,1-dimethylhydrazine, caffeine, and calcium cyclamate did not induce elevated levels of sperm abnormalities. The results suggest that sperm abnormalities might provide a rapid inexpensive mammalian screen for agents that lead to errors in the differentiation of spermatogenic stem cells in vivo and thus indicate agents which might prove to be mutagenic, teratogenic, or carcinogenic. Images PMID:1060122

  11. Crocidolite-induced pulmonary fibrosis in mice

    SciTech Connect

    Bowden, D.H.; Adamson, I.Y.R.

    1986-03-05

    The responses of alveolar and bronchial cells to asbestos exposure were studied to relate the cytokinetic changes of injury and repair to the inflammatory process and subsequent fibroblast activity. Lesions were induced by intratracheal instillation of 1 mg crocidolite asbestos to mice which were killed up to 20 weeks; /sup 3/H thymidine was injected 1 hr before death. A rapid inflammatory response with elevated PMN and lysosomal enzyme release was largely over by 2 wks though an increase in alveolar macrophages (AM) was maintained. Within 48 hrs there was multifocal necrosis of bronchiolar epithelium, maximal at bifurcations where longer fibers tend to adhere. Subsequently, intralumenal exudates were overgrown by proliferating epithelial cells and were incorporated, with long fibers, into bronchiolar connective tissue where granulomas formed. Alveolar lesions were located in peribronchiolar air sacs where focal injury of Type 1 cells by short fibers was rapidly repaired by division of Type 2 cells. Most short fibers were cleared by AMs, only a few fibers reached the interstitium. After 2 wks the increase in labeling index was due to labeled peribronchial fibroblasts. Biochemically, collagen increased after 4 wks when fibrosis was seen in bronchiolar lumens and in peribronchiolar connective tissue with lesser amounts in the centrilobular alveolar interstitium. The results suggest that long fibers induce bronchiolar injury and a more severe fibrotic pattern similar to human asbestosis.

  12. Narcosis studies and oxygen poisoning of mice

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The research for a mechanism by which narcotic gases alter metabolism is reported. Possible sites of action by narcotic and anesthetic gases in isolated electron transport particles were explored. Using the relative activities of the NADH-oxygen, NADH-ferricyanide, succinate-cytochrome C and succinate-NAD oxidoreductase systems as parameters, the relative potency of volatile anesthetics were tested. Testing the relative ability of human subjects to contract and repay an oxygen debt while in the narcotic versus alert state, it was found that narcosis induced by 33% nitrous oxide increased the size of the oxygen debt contracted and the amount of oxygen required to repay it during recovery. Mice acclimatized to sea level (760 mm Hg), 5000 feet (632 mm Hg) or 15,000 feet 437 mm Hg) for from one to eight weeks were found to be more susceptible to convulsion and death as a function of altitude acclimatization when tested in hyperoxic environments. There were no reasonable explanations for the connection between hypoxia and oxygen poisoning but several practical implications for persons living at altitude are discussed.

  13. Antioxidants can increase melanoma metastasis in mice.

    PubMed

    Le Gal, Kristell; Ibrahim, Mohamed X; Wiel, Clotilde; Sayin, Volkan I; Akula, Murali K; Karlsson, Christin; Dalin, Martin G; Akyürek, Levent M; Lindahl, Per; Nilsson, Jonas; Bergo, Martin O

    2015-10-01

    Antioxidants in the diet and supplements are widely used to protect against cancer, but clinical trials with antioxidants do not support this concept. Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors. However, little is known about the impact of antioxidant supplementation on the progression of other types of cancer, including malignant melanoma. We show that administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors. Similarly, NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression. PMID:26446958

  14. Oleuropein ameliorates acute colitis in mice.

    PubMed

    Giner, Elisa; Andújar, Isabel; Recio, M Carmen; Ríos, José Luis; Cerdá-Nicolás, José Miguel; Giner, Rosa M

    2011-12-28

    Oleuropein, the major secoiridoid in olive tree leaves, possesses a wide range of health promoting properties. It has recently been shown to exhibit anti-inflammatory activity. We have evaluated the effect of oleuropein on dextran sulfate sodium (DSS)-induced experimental colitis in mice in order to provide insight into its mechanisms of action. Oral administration of oleuropein notably attenuated the extent and severity of acute colitis while reducing neutrophil infiltration; production of NO, IL-1β, IL-6, and TNF-α; expression of iNOS, COX-2, and MMP-9; and the translocation of the NF-κB p65 subunit to the nucleus in colon tissue. In LPS-stimulated peritoneal macrophages, the oleuropein metabolite, hydroxytyrosol, was shown to inhibit NO production, iNOS expression, NF-κB p65 subunit translocation, mRNA expression, and the release of IL-1β, IL-6, and TNF-α. These results suggest that the effect of oleuropein on DSS-induced colitis is associated with a decrease in the production of interleukins and expression of proteins, principally through reduction of NF-κB activation. PMID:22114936

  15. Craniosynostosis in transgenic mice overexpressing Nell-1

    PubMed Central

    Zhang, Xinli; Kuroda, Shun’ichi; Carpenter, Dale; Nishimura, Ichiro; Soo, Chia; Moats, Rex; Iida, Keisuke; Wisner, Eric; Hu, Fei-Ya; Miao, Steve; Beanes, Steve; Dang, Catherine; Vastardis, Heleni; Longaker, Michael; Tanizawa, Katsuyuki; Kanayama, Norihiro; Saito, Naoaki; Ting, Kang

    2002-01-01

    Previously, we reported NELL-1 as a novel molecule overexpressed during premature cranial suture closure in patients with craniosynostosis (CS), one of the most common congenital craniofacial deformities. Here we describe the creation and analysis of transgenic mice overexpressing Nell-1. Nell-1 transgenic animals exhibited CS-like phenotypes that ranged from simple to compound synostoses. Histologically, the osteogenic fronts of abnormally closing/closed sutures in these animals revealed calvarial overgrowth and overlap along with increased osteoblast differentiation and reduced cell proliferation. Furthermore, anomalies were restricted to calvarial bone, despite generalized, non-tissue-specific overexpression of Nell-1. In vitro, Nell-1 overexpression accelerated calvarial osteoblast differentiation and mineralization under normal culture conditions. Moreover, Nell-1 overexpression in osteoblasts was sufficient to promote alkaline phosphatase expression and micronodule formation. Conversely, downregulation of Nell-1 inhibited osteoblast differentiation in vitro. In summary, Nell-1 overexpression induced calvarial overgrowth resulting in premature suture closure in a rodent model. Nell-1, therefore, has a novel role in CS development, perhaps as part of a complex chain of events resulting in premature suture closure. On a cellular level, Nell-1 expression may modulate and be both sufficient and required for osteoblast differentiation. PMID:12235118

  16. Chitinase Inhibition Promotes Atherosclerosis in Hyperlipidemic Mice

    PubMed Central

    Kitamoto, Shiro; Egashira, Kensuke; Ichiki, Toshihiro; Han, Xinbing; McCurdy, Sara; Sakuda, Shohei; Sunagawa, Kenji; Boisvert, William A.

    2014-01-01

    Chitinase 1 (CHIT1) is secreted by activated macrophages. Chitinase activity is raised in atherosclerotic patient sera and is present in atherosclerotic plaque. However, the role of CHIT1 in atherosclerosis is unknown. Preliminary studies of atherosclerosis in cynomolgous monkeys revealed CHIT1 to be closely correlated with areas of macrophage infiltration. Thus, we investigated the effects of a chitinase inhibitor, allosamidin, on macrophage function in vitro and on atherosclerotic development in vivo. In RAW264.7 cells, allosamidin elevated monocyte chemoattractant protein 1 and tumor necrosis factor alpha expression, and increased activator protein 1 and nuclear factor-κB transcriptional activity. Although inducible nitric oxide synthase, IL-6, and IL-1β expression were increased, Arg1 expression was decreased by chitinase inhibition, suggesting that suppression of CHIT1 activity polarizes macrophages into a M1 phenotype. Allosamidin decreased scavenger receptor AI, CD36, ABCA1, and ABCG1 expression which led to suppression of cholesterol uptake and apolipoprotein AI-mediated cholesterol efflux in macrophages. These effects were confirmed with CHIT1 siRNA transfection and CHIT1 plasmid transfection experiments in primary macrophages. Apolipoprotein E-deficient hyperlipidemic mice treated for 6 weeks with constant administration of allosamidin and fed an atherogenic diet showed aggravated atherosclerotic lesion formation. These data suggest that CHIT1 exerts protective effects against atherosclerosis by suppressing inflammatory responses and polarizing macrophages toward an M2 phenotype, and promoting lipid uptake and cholesterol efflux in macrophages. PMID:23685110

  17. piRNA and spermatogenesis in mice

    PubMed Central

    Chuma, Shinichiro; Nakano, Toru

    2013-01-01

    Transposable elements and their fossil sequences occupy about half of the genome in mammals. While most of these selfish mobile elements have been inactivated by truncations and mutations during evolution, some copies remain competent to transpose and/or amplify, posing an ongoing genetic threat. To control such mutagenic sequences, host genomes have developed multiple layers of defence mechanisms, including epigenetic regulation and RNA silencing. Germ cells, in particular, employ the piwi–small RNA pathway, which plays a central and adaptive role in safeguarding the germline genome from retrotransposons. Recent studies have revealed that a class of developmentally regulated genes, which have long been implicated in germ cell specification and differentiation, such as vasa and tudor family genes, play key roles in the piwi pathway to suppress retrotransposons, indicating that the piwi-mediated genome protection is at the core of germline development. Furthermore, while the piwi system primarily operates post-transcriptionally at the RNA level, it also affects the epigenetics of cognate genome loci, offering an intriguing link between small RNAs and transcriptional control in mammals. In this review, we summarize our current understanding of the piwi pathway in mice, which is emerging as a fundamental component of spermatogenesis that ensures male fertility and genome integrity. PMID:23166399

  18. Lupus susceptibility loci in New Zealand mice.

    PubMed Central

    Kono, D H; Burlingame, R W; Owens, D G; Kuramochi, A; Balderas, R S; Balomenos, D; Theofilopoulos, A N

    1994-01-01

    Susceptibility to systemic lupus erythematosus has been unequivocally established to be an inherited trait, but the exact genes and how they confer susceptibility remain largely unknown. In this study of (NZB x NZW)F2 intercross mice, we used linkage analysis of markers covering > 90% of the autosomal genome and identified eight susceptibility loci (Lbw1 to -8, chromosomes 17, 4-7, 18, 1, 11, respectively) associated with antichromatin autoantibody production, glomerulonephritis, and/or mortality. Only one locus, the major histocompatibility complex, was linked to all three traits. Two other loci were associated with both glomerulonephritis and mortality, whereas the remaining loci were linked to one of the above traits. Two additional loci (Sbw1 and -2) that contributed to splenomegaly were also identified. The Sbw2 locus mapped to the identical region as Lbw2, a locus on chromosome 4 linked to glomerulonephritis and mortality, suggesting a single locus with pleiotropic effects. The results indicate that the immunopathologic features of lupus are affected by distinct, but additive, genetic contributions. Studies to determine the nature of the genes associated with these loci should help define the genetic mechanisms involved in this systemic autoimmune disease. PMID:7937857

  19. Multiphysics Integrated Coupling Environment (MICE) User Manual

    SciTech Connect

    Varija Agarwal; Donna Post Guillen

    2013-08-01

    The complex, multi-part nature of waste glass melters used in nuclear waste vitrification poses significant modeling challenges. The focus of this project has been to couple a 1D MATLAB model of the cold cap region within a melter with a 3D STAR-CCM+ model of the melter itself. The Multiphysics Integrated Coupling Environment (MICE) has been developed to create a cohesive simulation of a waste glass melter that accurately represents the cold cap. The one-dimensional mathematical model of the cold cap uses material properties, axial heat, and mass fluxes to obtain a temperature profile for the cold cap, the region where feed-to-glass conversion occurs. The results from Matlab are used to update simulation data in the three-dimensional STAR-CCM+ model so that the cold cap is appropriately incorporated into the 3D simulation. The two processes are linked through ModelCenter integration software using time steps that are specified for each process. Data is to be exchanged circularly between the two models, as the inputs and outputs of each model depend on the other.

  20. Peromyscus (deer mice) as developmental models.

    PubMed

    Vrana, Paul B; Shorter, Kimberly R; Szalai, Gabor; Felder, Michael R; Crossland, Janet P; Veres, Monika; Allen, Jasmine E; Wiley, Christopher D; Duselis, Amanda R; Dewey, Michael J; Dawson, Wallace D

    2014-01-01

    Deer mice (Peromyscus) are the most common native North American mammals, and exhibit great natural genetic variation. Wild-derived stocks from a number of populations are available from the Peromyscus Genetic Stock Center (PGSC). The PGSC also houses a number of natural variants and mutants (many of which appear to differ from Mus). These include metabolic, coat-color/pattern, neurological, and other morphological variants/mutants. Nearly all these mutants are on a common genetic background, the Peromyscus maniculatus BW stock. Peromyscus are also superior behavior models in areas such as repetitive behavior and pair-bonding effects, as multiple species are monogamous. While Peromyscus development generally resembles that of Mus and Rattus, prenatal stages have not been as thoroughly studied, and there appear to be intriguing differences (e.g., longer time spent at the two-cell stage). Development is greatly perturbed in crosses between P. maniculatus (BW) and Peromyscus polionotus (PO). BW females crossed to PO males produce growth-restricted, but otherwise healthy, fertile offspring which allows for genetic analyses of the many traits that differ between these two species. PO females crossed to BW males produce overgrown but severely dysmorphic conceptuses that rarely survive to late gestation. There are likely many more uses for these animals as developmental models than we have described here. Peromyscus models can now be more fully exploited due to the emerging genetic (full linkage map), genomic (genomes of four stocks have been sequenced) and reproductive resources. PMID:24896658

  1. Of mice and men, metals and mutations.

    PubMed Central

    Danks, D M

    1986-01-01

    Several mutations affecting the transport of copper and zinc in humans and in mice have been discovered over the last 15 years, joining the long known disturbance of copper transport in Wilson's disease. Menkes' disease (classical and mild variant forms) and X linked Ehlers-Danlos syndrome (type IX, X linked cutis laxa) have features in common with one another and with the brindled (Mobr) and blotchy (Moblo) mouse mutants, respectively. There may be one allelic series of mutants in each species or two loci may be involved in each. The toxic milk mutant (tx) in the mouse may be homologous to Wilson's disease in man. The defect of intestinal absorption of zinc in acrodermatitis enteropathica has no homologue yet in the mouse. However, the lethal milk (lm) mutant in the mouse may be homologous to a condition of zinc deficiency described in a few breastfed, low birth weight infants. Many more genetic defects of transport of copper and of zinc may await discovery. Conversely, these mutants are valuable in elucidating the normal processes of copper and zinc transport. PMID:3519972

  2. Abnormal hematopoiesis in Gab2 mutant mice

    PubMed Central

    Zhang, Yi; Diaz-Flores, Ernesto; Li, Geqiang; Wang, Zhengqi; Kang, Zizhen; Haviernikova, Eleonora; Rowe, Sara; Qu, Cheng-Kui; Tse, William; Shannon, Kevin M.

    2007-01-01

    Gab2 is an important adapter molecule for cytokine signaling. Despite its major role in signaling by receptors associated with hematopoiesis, the role of Gab2 in hematopoiesis has not been addressed. We report that despite normal numbers of peripheral blood cells, bone marrow cells, and c-Kit+Lin?Sca-1+ (KLS) cells, Gab2-deficient hematopoietic cells are deficient in cytokine responsiveness. Significant reductions in the number of colony-forming units in culture (CFU-C) in the presence of limiting cytokine concentrations were observed, and these defects could be completely corrected by retroviral complementation. In earlier hematopoiesis, Gab2-deficient KLS cells isolated in vitro responded poorly to hematopoietic growth factors, resulting in an up to 11-fold reduction in response to a cocktail of stem cell factor, flt3 ligand, and thrombopoietin. Gab2-deficient c-Kit+Lin? cells also demonstrate impaired activation of extracellular signal-regulated kinase (ERK) and S6 in response to IL-3, which supports defects in activating the phosphatidylinositol-3 kinase (PI-3K) and mitogen-associated protein kinase (MAPK) signaling cascades. Associated with the early defects in cytokine response, competitive transplantation of Gab2?/? bone marrow cells resulted in defective long-term multilineage repopulation. Therefore, we demonstrate that Gab2 adapter function is intrinsically required for hematopoietic cell response to early-acting cytokines, resulting in defective hematopoiesis in Gab2-deficient mice. PMID:17374739

  3. Avoidance of hydrolyzed casein by mice

    PubMed Central

    Field, Kristin L.; Kimball, Bruce A.; Mennella, Julie A.; Beauchamp, Gary K.; Bachmanov, Alexander A.

    2008-01-01

    When casein, a milk protein, is hydrolyzed, it renders human foods that contain it (e.g., hypoallergenic infant formula, cheeses) distasteful to many people. This rejection of hydrolyzed casein (HC)-containing foods has recently been found to also occur in a non-human species (deer, Odocoileus spp.). Identifying other animals that avoid HC would facilitate understanding how and why HC-containing food is often rejected. This study determined whether HC-containing food is avoided by Mus musculus and whether consumption patterns were sensitive to testing conditions, specifically food form (powder, pellet or dough) and food access (ad libitum or 1.5 h/day following 6 h of food deprivation). Diets were offered in two-choice tests that paired an HC-containing food with an intact casein-containing alternative at seven protein concentrations (0%–50% w/w). Five experimental groups were tested under different combinations of food form and food access. Three groups (ad lib/powder, ad lib/pellet, and 1.5 h/pellet) avoided the HC diet starting at the 30% protein level. At the 40% and 50% protein levels, all groups showed strong avoidance of HC. Although testing conditions influenced total caloric intake and body weight gain, avoidance of HC at the highest concentrations was robust to the manipulations in experimental conditions. Our study suggests that mice may be a useful model for understanding the mechanisms of HC rejection. PMID:17900635

  4. Nonneoplastic nasal lesions in rats and mice.

    PubMed Central

    Monticello, T M; Morgan, K T; Uraih, L

    1990-01-01

    Rodents are commonly used for inhalation toxicology studies, but until recently the nasal passages have often been overlooked or only superficially examined. The rodent nose is a complex organ in which toxicant-induced lesions may vary, depending on the test compound. A working knowledge of rodent nasal anatomy and histology is essential for the proper evaluation of these responses. Lack of a systematic approach for examining rodent nasal tissue has led to a paucity of information regarding nonneoplastic lesions in the rodent nose. Therefore, slides from the National Toxicology Program (NTP) and the Chemical Industry Institute of Toxicology (CIIT) were examined, and the literature was reviewed to assemble the spectrum of nonneoplastic rodent nasal pathology. Presented are lesions associated with the various types of epithelia lining the rodent nasal cavity plus lesions involving accessory nasal structures. Even though there are anatomic and physiologic differences between the rodent and human nose, both rats and mice provide valuable animal models for the study of nasal epithelial toxicity, following administration of chemical compounds. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PLATE 17. PLATE 18. PLATE 19. PLATE 20. PLATE 21. PLATE 22. PLATE 23. PLATE 24. PLATE 25. PLATE 26. PLATE 27. PLATE 28. PLATE 29. PLATE 30. PLATE 31. PLATE 32. PLATE 33. PLATE 34. PLATE 35. PLATE 36. PLATE 37. PLATE 38. PMID:2200665

  5. Nitroglycerin Tolerance in Caveolin-1 Deficient Mice

    PubMed Central

    Mao, Mao; Varadarajan, Sudhahar; Fukai, Tohru; Bakhshi, Farnaz R.; Chernaya, Olga; Dudley, Samuel C.; Minshall, Richard D.; Bonini, Marcelo G.

    2014-01-01

    Nitrate tolerance developed after persistent nitroglycerin (GTN) exposure limits its clinical utility. Previously, we have shown that the vasodilatory action of GTN is dependent on endothelial nitric oxide synthase (eNOS/NOS3) activity. Caveolin-1 (Cav-1) is known to interact with NOS3 on the cytoplasmic side of cholesterol-enriched plasma membrane microdomains (caveolae) and to inhibit NOS3 activity. Loss of Cav-1 expression results in NOS3 hyperactivation and uncoupling, converting NOS3 into a source of superoxide radicals, peroxynitrite, and oxidative stress. Therefore, we hypothesized that nitrate tolerance induced by persistent GTN treatment results from NOS3 dysfunction and vascular toxicity. Exposure to GTN for 48–72 h resulted in nitrosation and depletion (>50%) of Cav-1, NOS3 uncoupling as measured by an increase in peroxynitrite production (>100%), and endothelial toxicity in cultured cells. In the Cav-1 deficient mice, NOS3 dysfunction was accompanied by GTN tolerance (>50% dilation inhibition at low GTN concentrations). In conclusion, GTN tolerance results from Cav-1 modification and depletion by GTN that causes persistent NOS3 activation and uncoupling, preventing it from participating in GTN-medicated vasodilation. PMID:25158065

  6. Nitroglycerin tolerance in caveolin-1 deficient mice.

    PubMed

    Mao, Mao; Varadarajan, Sudhahar; Fukai, Tohru; Bakhshi, Farnaz R; Chernaya, Olga; Dudley, Samuel C; Minshall, Richard D; Bonini, Marcelo G

    2014-01-01

    Nitrate tolerance developed after persistent nitroglycerin (GTN) exposure limits its clinical utility. Previously, we have shown that the vasodilatory action of GTN is dependent on endothelial nitric oxide synthase (eNOS/NOS3) activity. Caveolin-1 (Cav-1) is known to interact with NOS3 on the cytoplasmic side of cholesterol-enriched plasma membrane microdomains (caveolae) and to inhibit NOS3 activity. Loss of Cav-1 expression results in NOS3 hyperactivation and uncoupling, converting NOS3 into a source of superoxide radicals, peroxynitrite, and oxidative stress. Therefore, we hypothesized that nitrate tolerance induced by persistent GTN treatment results from NOS3 dysfunction and vascular toxicity. Exposure to GTN for 48-72 h resulted in nitrosation and depletion (>50%) of Cav-1, NOS3 uncoupling as measured by an increase in peroxynitrite production (>100%), and endothelial toxicity in cultured cells. In the Cav-1 deficient mice, NOS3 dysfunction was accompanied by GTN tolerance (>50% dilation inhibition at low GTN concentrations). In conclusion, GTN tolerance results from Cav-1 modification and depletion by GTN that causes persistent NOS3 activation and uncoupling, preventing it from participating in GTN-medicated vasodilation. PMID:25158065

  7. Interleukin-12 is not essential for silicosis in mice

    PubMed Central

    Davis, Gerald S; Pfeiffer, Linda M; Hemenway, David R; Rincon, Mercedes

    2006-01-01

    Background Silicosis features foci of inflammation where macrophages and lymphocytes precede and accompany fibroblast proliferation, alveolar epithelial hyperplasia, and increased deposition of connective tissue matrix material. In the mouse following silica inhalation there is recruitment of natural killer-, B-, and CD4+ and CD8+ lymphocytes to the alveolar spaces, enlargement of bronchial-associated lymphoid tissues (BALT), and aggregation of lymphocytes surrounding small airways and blood vessels. A substantial fraction of the recruited lung lymphocytes produce interferon-γ (IFN-γ), and IFN-γ gene-deleted mice develop less silicosis than wild-type mice. Interleukin-12 (IL-12) is an important pathway for driving the adaptive immune response towards a TH1-like phenotype. We hypothesized that IL-12 might stimulate lymphocyte activation and the up-regulation of IFN-γ, and consequently be an essential mediator for silicosis. Results C57Bl/6 wild-type (WT) and IL-12 deficient (IL-12 KO) mice were exposed to sham-air or crystobalite silica (61 mg/m3) by inhalation for 5 hours/day for 12 days and then studied from 1 to 112 days after exposure. Mice exposed to sham-air had normal lung histology at all time points. WT mice exposed to titanium dioxide (72 mg/m3) showed pulmonary macrophage recruitment but no increase in lung collagen. Both WT and IL-12 KO mice exposed to silica showed similar progressive lung pathology, increased wet lung weight and increased total lung collagen (hydroxyproline). IL-12 p35 mRNA was not increased in either strain after silica exposure; IL-12 p40 mRNA was up-regulated after silica in WT mice and constitutively absent in the IL-12 KO mice. IL-18 mRNA was not increased after silica exposure. The expression of IL-15 (an important driver for innate immunity, Natural Killer cell activation, and IFN-γ production) was abundant in air-exposed mice and was increased slightly in the lungs of mice with silicosis. Conclusion The axis of IL-12 driving IFN-γ production is not essential for the full manifestations of silicosis in mice exposed to a crystobalite silica aerosol. PMID:16396683

  8. Effectiveness of antimicrobial treatment against Borrelia burgdorferi infection in mice.

    PubMed Central

    Moody, K D; Adams, R L; Barthold, S W

    1994-01-01

    Although antimicrobial agents are effective therapy for early Lyme disease, optimal treatment schedules have not been conclusively established. The efficacy of various dosages of eight antibiotics used for borreliosis treatment was evaluated for C3H/HeNCrIBR mice, which reproducibly develop persistent infection, arthritis, and carditis when inoculated with Borrelia burgdorferi. Amoxicillin-clavulanic acid, ceftriaxone, and high-dose penicillin G effectively eliminated infection and disease. Oxytetracycline, doxycycline, chloramphenicol, erythromycin, and azithromycin failed to cure infected mice. There was a correlation between peak serum antibiotic concentrations in mice, as determined by agar well diffusion bioassays, and therapeutic levels in humans. When experimentally inoculated mice were treated at 1 week postinfection with ceftriaxone (16 mg/kg of body weight twice daily for 5 days) and monitored for up to 90 days, all treated mice were free of spirochetes and had no gross or histologic lesions. This antibiotic regimen at days 7 to 11 postinoculation eliminated the spirochetes so that there were no relapses during the 90-day observation period. For experimentally inoculated mice treated with ceftriaxone at 7 or 14 days postinfection, arthritis, carditis, and infection were eliminated. When treatment began at 30 and 90 days after inoculation, infection and active cardiac and arthritic lesions were eradicated; however, residual mild synovitis and vasculitis persisted in some mice. In comparison with inoculated, untreated mice, ceftriaxone therapy at 7, 14, 30, and 90 days postinfection abrogated the development of antibody titers against B. burgdorferi. Having the potential to determine the presence of the spirochete through culture and histologic lesions makes the B. burgdorferi-inoculated C3H mouse model a valuable adjunct in evaluating chemotherapeutic options for Lyme disease. PMID:7979290

  9. Surgery plus anesthesia induces loss of attention in mice

    PubMed Central

    Ren, Quan; Peng, Mian; Dong, Yuanlin; Zhang, Yiying; Chen, Ming; Yin, Ning; Marcantonio, Edward R.; Xie, Zhongcong

    2015-01-01

    There is a need to develop animal models to study postoperative delirium. Inattention is one of the symptoms of delirium. Increases in the levels of α-synuclein and S100β have been reported to be associated with delirium. Therefore, we set out to determine the effects of surgery plus general anesthesia on the behavioral changes (including loss of attention) in mice and on the levels of α-synuclein and S100β in the brain tissues of these mice. C57BL/6J mice (2- to 8-months-old) had a simple laparotomy plus isoflurane anesthesia. The behavioral changes, including attention level and the speed of movements, were determined 12, 24, and 48 h after the surgery plus anesthesia in the mice. The levels of α-synuclein and S100β in the cortex of these mice following the surgery plus anesthesia were determined by Western blot analysis. We found that there was a loss of attention at 24, but not 12 or 48 h following the surgery plus anesthesia (49% ± 5 vs. 33% ± 2.9, P = 0.011, N = 12) in the mice without significantly affecting the speed of their movements. There were increases in the levels of total α-synuclein (139% ± 33.5 vs. 100% ± 13.7, P = 0.037, N = 6) and S100β (142% ± 7.7 vs. 100% ± 6, P = 0.002, N = 6) in the cortex of the mice 12 h following the surgery plus anesthesia. These findings suggested that the surgery plus isoflurane anesthesia might induce behavioral and biochemical/cellular changes associated with delirium. We could use the surgery plus anesthesia in mice to develop an animal model to study postoperative delirium. PMID:26441522

  10. Mig6 haploinsufficiency protects mice against streptozotocin-induced diabetes

    PubMed Central

    Chen, Yi-Chun; Colvin, E. Scott; Griffin, Katherine E.; Maier, Bernhard F.; Fueger, Patrick T.

    2014-01-01

    Aims/hypothesis EGF and gastrin co-administration reverses type 1 diabetes in rodent models. However, the failure of this to translate into a clinical treatment suggests that EGF-mediated tissue repair is a complicated process and warrants further investigation. Thus, we aimed to determine whether EGF receptor (EGFR) feedback inhibition by mitogen-inducible gene 6 protein (MIG6) limits the effectiveness of EGF therapy and promotes type 1 diabetes development. Methods We treated Mig6 (also known as Errfi1) haploinsufficient mice (Mig6+/−) and their wild-type littermates (Mig6+/+) with multiple low doses of streptozotocin (STZ), and monitored diabetes development via glucose homeostasis tests and histological analyses. We also investigated MIG6-mediated cytokine-induced desensitisation of EGFR signalling and the DNA damage repair response in 832/13 INS-1 beta cells. Results Whereas STZ-treated Mig6+/+ mice became diabetic, STZ-treated Mig6+/− mice remained glucose tolerant. In addition, STZ-treated Mig6+/− mice exhibited preserved circulating insulin levels following a glucose challenge. As insulin sensitivity was similar between Mig6+/− and Mig6+/+ mice, the preserved glucose tolerance in STZ-treated Mig6+/− mice probably results from preserved beta cell function. This is supported by elevated Pdx1 and Irs2 mRNA levels in islets isolated from STZ-treated Mig6+/− mice. Conversely, MIG6 overexpression in isolated islets compromises glucose-stimulated insulin secretion. Studies in 832/13 cells suggested that cytokine-induced MIG6 hinders EGFR activation and inhibits EGF-mediated DNA damage repair. STZ-treated Mig6+/− mice also have increased beta cell mass recovery. Conclusions/interpretation Reducing Mig6 expression promotes beta cell repair and abates the development of experimental diabetes, suggesting that MIG6 may be a novel therapeutic target for preserving beta cells. PMID:24989997

  11. Diet and cancer prevention studies in p53-deficient mice.

    PubMed

    Hursting, S D; Perkins, S N; Phang, J M; Barrett, J C

    2001-11-01

    Progress in mechanism-based cancer prevention research may be facilitated by the use of animal models displaying specific genetic susceptibilities for cancer such as mice deficient in the p53 tumor suppressor gene, the most frequently altered gene in human cancer. We observed in p53-knockout (p53-/-) mice that calorie restriction (CR; 60% of the control group's intake of carbohydrate energy) increased the latency of spontaneous tumor development (mostly lymphomas) approximately 75%, decreased serum insulin-like growth factor (IGF)-1 and leptin levels, significantly slowed thymocyte cell cycle traverse and induced apoptosis in immature thymocytes. In heterozygous p53-deficient (p53+/-) mice, CR and 1 d/wk of food deprivation each significantly delayed spontaneous tumor development (a mix of lymphomas, sarcomas and epithelial tumors) and decreased serum IGF-1 and leptin levels even when begun late in life. We have also developed a rapid and relevant p53+/- mouse mammary tumor model by crossing p53-deficient mice with MMTV-Wnt-1 transgenic mice, and found that CR and 1 d/wk food deprivation significantly increased mammary tumor latency (greater than twofold) and reduced the mean serum IGF-1 and leptin levels to <50% of that of control mice (P < 0.0001). In addition, fluasterone, fenretinide and soy each delayed tumor development but had little effect on IGF-1 or leptin levels. We have capitalized on the susceptibility of p53+/- mice to chronic, low dose, aromatic amine-induced bladder carcinogenesis to develop a useful model for evaluating bladder cancer prevention approaches such as cyclooxygenase-2 inhibition. As demonstrated by these examples, mice with specific (and human-like) genetic susceptibilities for cancer provide powerful new tools for testing and characterizing interventions that may inhibit the process of carcinogenesis in humans. PMID:11694654

  12. Crybb2 deficiency impairs fertility in female mice

    SciTech Connect

    Gao, Qian; Sun, Li-Li; Xiang, Fen-Fen; Gao, Li; Jia, Yin; Zhang, Jian-Rong; Tao, Hai-Bo; Zhang, Jun-Jie; Li, Wen-Jie

    2014-10-10

    Highlights: • Crybb2 deletion impaired female fertility. • Crybb2 deletion dramatically affected the production of reproduction-related hormones and hormone response. • Crybb2 deletion impaired follicular development and inhibited the proliferation of granulosa cells. • Crybb2 deletion promoted follicular atresia and apoptosis in granulosa cells. - Abstract: Beta-B2-crystallin (CRYBB2), encoded by Crybb2 gene, is a major protein in the mammalian eye lens that plays an important role in maintaining the transparency of the ocular lens. However, CRYBB2 also plays important roles in many extra-lenticular tissues and organs such as the retina, brain and testis. Our previous studies demonstrated that male Crybb2 deficient (Crybb2{sup −/−}) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2{sup −/−} mice exhibited reduced ovary weights and shorter estrous cycle percentages. Here we specifically investigated the role of CRYBB2 in the female reproductive system. Our studies revealed that ovaries from female Crybb2{sup −/−} mice exhibited significantly reduced numbers of primordial, secondary and pre-ovulatory follicles when compared with WT mice, while the rate of atretic follicles was also increased. Additionally, fewer eggs were collected from the oviduct of Crybb2{sup −/−} female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of female Crybb2{sup −/−} mice, while progesterone levels were lower in diestrus cycles. Furthermore, the expression of survival and cell cycle genes, Bcl-2, Cdk4 and Ccnd2, were significantly decreased in granulosa cells isolated from female Crybb2{sup −/−} mice, consistent with the predominant expression of CRYBB2 in ovarian granulosa cells. Our results reveal a critical role for CRYBB2 in female fertility and specific effects on the proliferation and survival status of ovarian granulosa cells.

  13. Postural and locomotor control in normal and vestibularly deficient mice

    PubMed Central

    Vidal, P-P; Degallaix, L; Josset, P; Gasc, J-P; Cullen, K E

    2004-01-01

    We investigated how vestibular information is used to maintain posture and control movement by studying vestibularly deficient mice (IsK−/− mutant). In these mutants, microscopy showed degeneration of the cristae of the semicircular canals and of the maculae of the utriculi and sacculi, while behavioural and vestibulo-ocular reflex testing showed that vestibular function was completely absent. However, the histology of Scarpa's ganglia and the vestibular nerves was normal in mutant mice, indicating the presence of intact central pathways. Using X-ray and high-speed cineradiography, we compared resting postures and locomotion patterns between these vestibularly deficient mice and vestibularly normal mice (wild-type and IsK+/−). The absence of vestibular function did not affect resting posture but had profound effects on locomotion. At rest, the S-shaped, sagittal posture of the vertebral column was the same for wild-type and mutant mice. Both held the head with the atlanto-occipital joint fully flexed, the cervico-thoracic junction fully flexed, and the cervical column upright. Wild-type mice extended the head and vertebral column and could walk in a straight line. In marked contrast, locomotion in vestibularly deficient mice was characterized by circling episodes, during which the vertebral column maintained an S-shaped posture. Thus, vestibular information is not required to control resting posture but is mandatory for normal locomotion. We propose that vestibular inputs are required to signal the completion of a planned trajectory because mutant mice continued rotating after changing heading direction. Our findings support the hypothesis that vertebrates limit the number of degrees of freedom to be controlled by adopting just a few of the possible skeletal configurations. PMID:15243133

  14. Abnormal fluid homeostasis in apelin receptor knockout mice

    PubMed Central

    Roberts, Emma M; Newson, Michael J F; Pope, George R; Landgraf, Rainer; Lolait, Stephen J; O'Carroll, Anne-Marie

    2009-01-01

    The apelinergic system, comprised of apelin and its G protein-coupled receptor (APJ; APLNR as given in MGI Database), is expressed within key regions of the central nervous system associated with arginine vasopressin (AVP) synthesis and release as well as in structures involved in the control of drinking behaviour, including the magnocellular neurones of the hypothalamus, circumventricular organs, and the pituitary gland. This localisation is indicative of a possible functional role in fluid homeostasis. We investigated a role for APJ in the regulation of fluid balance using mice deficient for the receptor. Male APJ wild-type and knockout (APJ−/−) mice were housed in metabolic cages to allow determination of water intake and urine volume and osmolality. When provided with free access to water, APJ−/− mice drank significantly less than wild-types, while their urine volume and osmolality did not differ. Water deprivation for 24 h significantly reduced urine volume and increased osmolality in wild-type but not in APJ−/− mice. Baseline plasma AVP concentration increased comparably in both wild-type and APJ−/− mice following dehydration; however, APJ−/− mice were unable to concentrate their urine to the same extent as wild-type mice in response to the V2 agonist desmopressin. Analysis of c-fos (Fos as given in MGI Database) mRNA expression in response to dehydration showed attenuation of expression within the subfornical organ, accentuated expression in the paraventricular nucleus, but no differences in expression in the supraoptic nucleus nor median pre-optic nucleus in APJ−/− mice compared with wild-type. These findings demonstrate a physiological role for APJ in mechanisms of water intake and fluid retention and suggest an anti-diuretic effect of apelin in vivo. PMID:19578099

  15. Complement deficiency promotes cutaneous wound healing in mice

    PubMed Central

    Rafail, Stavros; Kourtzelis, Ioannis; Foukas, Periklis G.; Markiewski, Maciej M.; DeAngelis, Robert A.; Guariento, Mara; Ricklin, Daniel; Grice, Elizabeth A.; Lambris, John D.

    2014-01-01

    Wound healing is a complex homeostatic response to injury that engages numerous cellular activities, processes, and cell-to-cell interactions. The complement system, an intricate network of proteins with important roles in immune surveillance and homeostasis, has been implicated in many physiological processes; however, its role in wound healing remains largely unexplored. Here we employ a murine model of excisional cutaneous wound healing and show that C3−/− mice exhibit accelerated early stages of wound healing. Reconstitution of C3−/− mice with serum from C3+/+ mice or purified human C3 abrogated the accelerated wound healing phenotype. Wound histology of C3−/− mice revealed a reduction in inflammatory infiltrate compared to C3+/+ mice. C3 deficiency also resulted in increased accumulation of mast cells and advanced angiogenesis. We further show that mice deficient in the downstream complement effector C5 exhibit a similar wound healing phenotype, which is recapitulated in C5aR1−/− mice, but not C3aR−/− or C5aR2−/− mice. Taken together, these data suggest that C5a signaling through C5aR may in part play a pivotal role in recruitment and activation of inflammatory cells to the wound environment, which in turn could delay the early stages of cutaneous wound healing. These findings also suggest a previously underappreciated role for complement in wound healing, and may have therapeutic implications for conditions of delayed wound healing. PMID:25548229

  16. Maotai ameliorates diethylnitrosamine-initiated hepatocellular carcinoma formation in mice.

    PubMed

    Yi, Xu; Long, Li; Yang, Chunzhang; Lu, Yingying; Cheng, Mingliang

    2014-01-01

    Consumption of alcohol is closely related to liver disease, such as hepatic fibrosis or even hepatocellular carcinoma (HCC). However, epidemiological and experimental studies indicated that consumption of Maotai, one of the famous liquors in China, exhibits no significant correlation with hepatic fibrosis or cirrhosis as other beverage sources do. This study detected the relationship of Maotai consumption and HCC development in a diethylnitrosamine (DEN)-initiated HCC animal model. DEN was given to mice at a dose of 100 mg/kg, ip, and 50 mg/kg, ip in the following week. Mice were simultaneously given Maotai or an equal amount of ethanol (53%, 5 ml/kg/day, 5 days/week for up to 35 weeks). At 3-week and 35- week of the experiment, serum and livers were collected for biochemical and histopathological examination of liver injury and incidence of HCC. Real-time RT-PCR, immunohistochemistry and Western blotting were used to examine the expression of metallothionein-1/2 (MT-1/2), NF-E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit (GCLC) and modified subunit (GCLM). We identified tissue damage and dysfunction of liver in ethanol + DEN-treated mice, whereas the extent of injury was reduced in Maotai+ DEN -treated mice. Significant Glypican-3(GPC3) expression and precancerous injury or HCC were seen in approximately 50% of mice with ethanol+ DEN, but barely be seen in Maotai + DEN-treated mice. A higher expression of MT-1/2, Nrf2 and GCLC could be seen in Maotai + DEN-treated mice. Thus, Maotai liquor ameliorates the formation of DEN-induced HCC in mice, and the protection mechanism is possibly related with the activation of anti-oxidation factors, such as MTs, Nrf2 and GCLC. PMID:24690765

  17. Moxidectin Toxicity in Senescence-Accelerated Prone and Resistant Mice

    PubMed Central

    Lee, Vanessa K; Tiwary, Asheesh K; Sharma-Reddy, Prachi; Lieber, Karen A; Taylor, Douglas K; Mook, Deborah M

    2009-01-01

    Moxidectin has been used safely as an antiparasitic in many animal species, including for the eradication of the mouse fur mite, Mycoptes musculinus. Although no side effects of moxidectin have previously been reported to occur in mice, 2 strains of the senescence-accelerated mouse (SAMP8 and SAMR1) sustained considerable mortality after routine prophylactic treatment. To investigate the mechanism underlying this effect, moxidectin toxicosis in these mice was evaluated in a controlled study. Moxidectin was applied topically (0.015 mg), and drug concentrations in both brain and serum were analyzed by using HPLC coupled with mass spectrometry. The moxidectin concentration in brain of SAMP8 mice was 18 times that in controls, and that in brain of SAMR1 mice was 14 times higher than in controls, whereas serum moxidectin concentrations did not differ significantly among the 3 strains. Because deficiency of the blood–brain barrier protein P-glycoprotein leads to sensitivity to this class of drugs in other SAM mice, Pgp immunohistochemistry of brain sections from a subset of mice was performed to determine whether this commercially available analysis could predict sensitivity to this class of drug. The staining analysis showed no difference among the strains of mice, indicating that this test does not correlate with sensitivity. In addition, no gross or histologic evidence of organ toxicity was found in brain, liver, lung, or kidney. This report shows that topically applied moxidectin at a standard dose accumulates in the CNS causing toxicosis in both SAMP8 and SAMR1 mice. PMID:19619412

  18. Environmental enrichment does not impact on tumor growth in mice

    PubMed Central

    Kershaw, Michael H

    2013-01-01

    The effect of environmental enrichment (EE) on a variety of physiologic and disease processes has been studied in laboratory mice. During EE, a large group of mice are housed in larger cages than the standard cage and are given toys and equipment, enabling more social contact, and providing a greater surface area per mouse, and a more stimulating environment. Studies have been performed into the effect of EE on neurogenesis, brain injury, cognitive capacity, memory, learning, neuronal pathways, diseases such as Alzheimer’s, anxiety, social defeat, emotionality, depression, drug addiction, alopecia, and stereotypies. In the cancer field, three papers have reported effects on mice injected with tumors and housed in enriched environments compared with those housed in standard conditions. One paper reported a significant decrease in tumor growth in mice in EE housing. We attempted to replicate this finding in our animal facility, because the implications of repeating this finding would have profound implications for how we house all our mice in our studies on cancer. We were unable to reproduce the results in the paper in which B16F10 subcutaneous tumors of mice housed in EE conditions were smaller than those of mice housed in standard conditions. The differences in results could have been due to the different growth rate of the B16F10 cultures from the different laboratories, the microbiota of the mice housed in the two animal facilities, variations in noise and handling between the two facilities, food composition, the chemical composition of the cages or the detergents used for cleaning, or a variety of other reasons. EE alone does not appear to consistently result in decreased tumor growth, but other factors would appear to be able to counteract or inhibit the effects of EE on cancer progression. PMID:24555065

  19. Variant-specific immunity to Plasmodium berghei in pregnant mice.

    PubMed

    Megnekou, Rosette; Hviid, Lars; Staalsoe, Trine

    2009-05-01

    We have investigated the immunological basis of pregnancy-related Plasmodium berghei recrudescence in immune mice with substantial preexisting immunity. Specifically, we examined the relevance of this experimental model to the study of pregnancy-associated malaria (PAM) caused by P. falciparum in women with substantial preexisting protective immunity. We used mice with immunity induced prior to pregnancy and employed flow cytometry to assess their levels of immunoglobulin G (IgG) recognizing antigens on the surfaces of infected erythrocytes (IEs) in plasma. After immunization, the mice did not possess IgG specific for antigens on IEs obtained during pregnancy-related recrudescence but they acquired recrudescence-specific IgG over the course of several pregnancies and recrudescences. In contrast, levels of antibodies recognizing IEs from nonpregnant mice did not increase with increasing parity. Furthermore, maternal hemoglobin levels increased and pregnancy-related parasitemia decreased with increasing parity. Finally, parasitemic mice produced smaller litters and pups with lower weights than nonparasitemic mice. Taken together, these observations suggest that levels of antibodies specific for recrudescence-type IEs are related to the protection of pregnant mice from maternal anemia, low birth weight, and decreased litter size. We conclude that the model replicates many of the key parasitological and immunological features of PAM, although the P. berghei genome does not encode proteins homologous to the P. falciparum erythrocyte membrane protein 1 adhesins, which are of key importance in P. falciparum malaria. The study of P. berghei malaria in pregnant, immune mice can be used to gain significant new insights regarding malaria pathogenesis and immunity in general and regarding PAM in particular. PMID:19237516

  20. Pirt contributes to uterine contraction-induced pain in mice.

    PubMed

    Wang, Changming; Wang, Zhongli; Yang, Yan; Zhu, Chan; Wu, Guanyi; Yu, Guang; Jian, Tunyu; Yang, Niuniu; Shi, Hao; Tang, Min; He, Qian; Lan, Lei; Liu, Qin; Guan, Yun; Dong, Xinzhong; Duan, Jinao; Tang, Zongxiang

    2015-01-01

    Uterine contraction-induced pain (UCP) represents a common and severe form of visceral pain. Nerve fibers that innervate uterine tissue express the transient receptor potential vanilloid channel 1 (TRPV1), which has been shown to be involved in the perception of UCP. The phosphoinositide-interacting regulator of TRP (Pirt) may act as a regulatory subunit of TRPV1. The intraperitoneal injection of oxytocin into female mice after a 6-day priming treatment with estradiol benzoate induces writhing responses, which reflect the presence of UCP. Here, we first compared writhing response between Pirt (+/+) and Pirt (-/-) mice. Second, we examined the innervation of Pirt-expressing nerves in the uterus of Pirt (-/-) mice by immunofluorescence and two-photon microscopy. Third, we identified the soma of dorsal root ganglion (DRG) neurons that innerve the uterus using retrograde tracing and further characterized the neurochemical properties of these DRG neurons. Finally, we compared the calcium response of capsaicin between DRG neurons from Pirt (+/+) and Pirt (-/-) mice. We found that the writhing responses were less intensive in Pirt (-/-) mice than in Pirt (+/+) mice. We also observed Pirt-expressing nerve fibers in the myometrium of the uterus, and that retrograde-labeled cells were small-diameter, unmyelinated, and Pirt-positive DRG neurons. Additionally, we found that the number of capsaicin-responding neurons and the magnitude of evoked calcium response were markedly reduced in DRG neurons from Pirt (-/-) mice. Taken together, we speculate that Pirt plays an important role in mice uterine contraction-induced pain. PMID:26376721

  1. Immune response to intrapharyngeal LPS in neonatal and juvenile mice.

    PubMed

    McGrath-Morrow, Sharon A; Lee, Seakwoo; Gibbs, Kevin; Lopez, Armando; Collaco, Joseph M; Neptune, Enid; Soloski, Mark J; Scott, Alan; D'Alessio, Franco

    2015-03-01

    Neonates and infants have a higher morbidity and mortality associated with lower respiratory tract illnesses compared with older children. To identify age-related and longitudinal differences in the cellular immune response to acute lung injury (ALI), neonatal and juvenile mice were given Escherichia coli LPS using a novel, minimally invasive aspiration technique. Neonatal and juvenile mice received between 3.75 and 7.5 mg/kg LPS by intrapharyngeal aspiration. Airway and lung cells were isolated and characterized by flow cytometry, cytokine/chemokine mRNA expression from lung homogenates was quantified, and lung morphometry and injury scores were performed. LPS-treated neonatal mice underwent adoptive transfer with adult T regulatory cells (Tregs). After LPS aspiration, lung monocytes isolated from neonatal mice had a predominant M2 phenotype, whereas lung monocytes from juvenile mice displayed a mixed M1/M2 phenotype. At 72 hours after LPS exposure, neonatal lungs were slower to resolve inflammation and expressed lower mRNA levels of CCL2, CCL5, CXCL10, and IL-10. Juvenile, but not neonatal, mice demonstrated a significant increase in airway Tregs after LPS exposure. Adoptive transfer of adult Tregs into LPS-challenged neonatal mice resulted in reduced lung inflammation and improved weight gain. These findings underscore several vulnerabilities in the neonatal immune response to LPS-induced ALI. Most striking was the deficiency in airway Tregs after LPS aspiration. Adoptive transfer of adult Tregs mitigated LPS-induced ALI in neonatal mice, highlighting the importance of age-related differences in Tregs and their response to ALI during early postnatal development. PMID:25068533

  2. Maotai Ameliorates Diethylnitrosamine-Initiated Hepatocellular Carcinoma Formation in Mice

    PubMed Central

    Yi, Xu; Long, Li; Yang, Chunzhang; Lu, Yingying; Cheng, Mingliang

    2014-01-01

    Consumption of alcohol is closely related to liver disease, such as hepatic fibrosis or even hepatocellular carcinoma (HCC). However, epidemiological and experimental studies indicated that consumption of Maotai, one of the famous liquors in China, exhibits no significant correlation with hepatic fibrosis or cirrhosis as other beverage sources do. This study detected the relationship of Maotai consumption and HCC development in a diethylnitrosamine (DEN)-initiated HCC animal model. DEN was given to mice at a dose of 100 mg/kg, ip, and 50 mg/kg, ip in the following week. Mice were simultaneously given Maotai or an equal amount of ethanol (53%, 5 ml/kg/day, 5days/week for up to 35weeks). At 3-week and 35- week of the experiment, serum and livers were collected for biochemical and histopathological examination of liver injury and incidence of HCC. Real-time RT-PCR, immunohistochemistry and Western blotting were used to examine the expression of metallothionein-1/2 (MT-1/2), NF-E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit (GCLC) and modified subunit (GCLM). We identified tissue damage and dysfunction of liver in ethanol + DEN-treated mice, whereas the extent of injury was reduced in Maotai+ DEN –treated mice. Significant Glypican-3(GPC3) expression and precancerous injury or HCC were seen in approximately 50% of mice with ethanol+ DEN, but barely be seen in Maotai + DEN-treated mice. A higher expression of MT-1/2, Nrf2 and GCLC could be seen in Maotai + DEN-treated mice. Thus, Maotai liquor ameliorates the formation of DEN-induced HCC in mice, and the protection mechanism is possibly related with the activation of anti-oxidation factors, such as MTs, Nrf2 and GCLC. PMID:24690765

  3. Chimeric plantibody passively protects mice against aerosolized ricin challenge.

    PubMed

    Sully, Erin K; Whaley, Kevin J; Bohorova, Natasha; Bohorov, Ognian; Goodman, Charles; Kim, Do H; Pauly, Michael H; Velasco, Jesus; Hiatt, Ernie; Morton, Josh; Swope, Kelsi; Roy, Chad J; Zeitlin, Larry; Mantis, Nicholas J

    2014-05-01

    Recent incidents in the United States and abroad have heightened concerns about the use of ricin toxin as a bioterrorism agent. In this study, we produced, using a robust plant-based platform, four chimeric toxin-neutralizing monoclonal antibodies that were then evaluated for the ability to passively protect mice from a lethal-dose ricin challenge. The most effective antibody, c-PB10, was further evaluated in mice as a therapeutic following ricin exposure by injection and inhalation. PMID:24574537

  4. Effects of reduced food intake on reproduction in mice.

    PubMed

    Zamiri, M J

    1978-12-01

    The effect of undernutrition on the reproductive performance of the Quackenbush strain of mice was studied using four dietary levels: ad libitum (8.0 g per mouse per day; D100), 85% (D85), 70% (D70), and 55% (D55) of ad libitum food intake. Dietary restriction for 60 days at the 55% level resulted in an increase in the length of the oestrous cycle compared with other dietary levels, whereas D85 and D70 mice did not differ from the control group. When the underfed mice were fed ad libitum their reproductive performance did not differ from that of the D100 mice. In a second experiment mice were fed the restricted diet for 2 weeks before males were introduced. The males were fed ad libitum except for a 5-day mating period, when they were removed and replaced by another group of males. On days 1, 7, and 16 of pregnancy approximatley 10 mice per dietary level were killed and the ovulation rate, implantation rate, and late embryonic survival were estimated. The remainder of the mice were allowed to litter for studies of the litter size, birth weight and sex ratio. Dietary restriction did not affect the ovulation rate and only 45% restriction resulted in a decreased implantation rate. The late embryonic survival was reduced at all levels of restricted food intake, but sex ratios were unaffected by dietary intake. Dietary restriction of 30% and 45% decreased the littering rate and increased foetal resorption. The litter size decreased at all levels of dietary restrictions, but the birth weight was reduced only with moderate (D70) and severe (D55) restrictions. The litter size and the pup weight of the D70 and D55 mice following ad libitum refeeding were greater than those of their counterparts maintained on restricted feeding. PMID:754684

  5. Environmental enrichment does not impact on tumor growth in mice.

    PubMed

    Westwood, Jennifer A; Darcy, Phillip K; Kershaw, Michael H

    2013-01-01

    The effect of environmental enrichment (EE) on a variety of physiologic and disease processes has been studied in laboratory mice. During EE, a large group of mice are housed in larger cages than the standard cage and are given toys and equipment, enabling more social contact, and providing a greater surface area per mouse, and a more stimulating environment. Studies have been performed into the effect of EE on neurogenesis, brain injury, cognitive capacity, memory, learning, neuronal pathways, diseases such as Alzheimer's, anxiety, social defeat, emotionality, depression, drug addiction, alopecia, and stereotypies. In the cancer field, three papers have reported effects on mice injected with tumors and housed in enriched environments compared with those housed in standard conditions. One paper reported a significant decrease in tumor growth in mice in EE housing. We attempted to replicate this finding in our animal facility, because the implications of repeating this finding would have profound implications for how we house all our mice in our studies on cancer. We were unable to reproduce the results in the paper in which B16F10 subcutaneous tumors of mice housed in EE conditions were smaller than those of mice housed in standard conditions. The differences in results could have been due to the different growth rate of the B16F10 cultures from the different laboratories, the microbiota of the mice housed in the two animal facilities, variations in noise and handling between the two facilities, food composition, the chemical composition of the cages or the detergents used for cleaning, or a variety of other reasons. EE alone does not appear to consistently result in decreased tumor growth, but other factors would appear to be able to counteract or inhibit the effects of EE on cancer progression. PMID:24555065

  6. The origin of (+)-tubocurarine resistance in dystrophic mice.

    PubMed Central

    Kelly, S. S.; Morgan, G. P.; Smith, J. W.

    1986-01-01

    Intracellular recording, twitch responses and radio-ligand binding techniques were used to study the causes of resistance to (+)-tubocurarine (curare) of extensor digitorum longus (EDL) muscles from dystrophic mice (129 ReJ/strain). The indirectly evoked twitch response of muscles from dystrophic mice was more resistant to block by curare than the twitch response of muscles from normal littermates. The IC50 (concentration producing 50% inhibition of stimulus-evoked contractions) values for the curare block of muscle twitch were 0.78 +/- 0.03 microM and 1.32 +/- 0.05 microM (mean +/- 95% confidence limits) for muscles from normal and dystrophic mice, respectively. There was no difference between muscles from normal and dystrophic mice in the number of alpha-bungarotoxin binding sites per endplate. The amplitudes of both spontaneous miniature endplate potentials (m.e.p.ps) in unblocked preparations and of evoked endplate potentials (e.p.ps) in 1.91 microM curare were greater in muscles from dystrophic mice than in muscles from normal mice. The ratio dystrophic/normal was greater for the e.p.p. amplitudes than for the m.e.p.p. amplitudes. The quantum content of e.p.ps in magnesium-blocked and in cut-fibre preparations was greater in muscles from dystrophic mice than in muscles from normal littermates. Calculation of the binomial parameters n and p in the cut-fibre preparations indicated that this increased quantum content was caused by an increase in the value of p. It is concluded that at least part of the increased resistance to curare of the indirectly evoked twitch response of muscles from dystrophic mice is due to an increase in the quantum content of e.p.ps in these muscles. PMID:3801778

  7. Scrapie Pathogenesis in Subclinically Infected B-Cell-Deficient Mice

    PubMed Central

    Frigg, Rico; Klein, Michael A.; Hegyi, Ivan; Zinkernagel, Rolf M.; Aguzzi, Adriano

    1999-01-01

    Prion infections can present without clinical manifestations. B-cell deficiency may be a model for subclinical transmissible spongiform encephalopathy, since it protects mice from disease upon intraperitoneal administration of scrapie prions; however, a proportion of B-cell-deficient mice accumulate protease-resistant prion protein in their brains. Here, we have characterized this subclinical disease. In addition, we have studied the possibility that a neurotoxic factor secreted by B cells may contribute to pathogenesis. PMID:10516067

  8. Transgenic and knockout mice in research on prion diseases.

    PubMed

    Raeber, A J; Brandner, S; Klein, M A; Benninger, Y; Musahl, C; Frigg, R; Roeckl, C; Fischer, M B; Weissmann, C; Aguzzi, A

    1998-10-01

    Since the discovery of the prion protein (PrP) gene more than a decade ago, transgenetic investigations on the PrP gene have shaped the field of prion biology in an unprecedented way. Many questions regarding the role of PrP in susceptibility of an organism exposed to prions have been elucidated. For example mice with a targeted disruption of the PrP gene have allowed the demonstration that an organism that lacks PrPc is resistant to infection by prions. Reconstitution of these mice with mutant PrP genes allowed investigations on the structure-activity relationship of the PrP gene with regard to scrapie susceptibility. Unexpectedly, transgenic mice expressing PrP with specific amino-proximal truncations spontaneously develop a neurologic syndrome presenting with ataxia and cerebellar lesions. A distinct spontaneous neurologic phenotype was observed in mice with internal deletions in PrP. Using ectopic expression of PrP in PrP knockout mice has turned out to be a valuable approach towards the identification of host cells that are capable of replicating prions. Transgenic mice have also contributed to our understanding of the molecular basis of the species barrier for prions. Finally, the availability of PrP knockout mice and transgenic mice overexpressing PrP allows selective reconstitution experiments aimed at expressing PrP in neurografts or in specific populations of hemato- and lymphopoietic cells. Such studies have shed new light onto the mechanisms of prion spread and disease pathogenesis. PMID:9804380

  9. Scrapie pathogenesis in subclinically infected B-cell-deficient mice.

    PubMed

    Frigg, R; Klein, M A; Hegyi, I; Zinkernagel, R M; Aguzzi, A

    1999-11-01

    Prion infections can present without clinical manifestations. B-cell deficiency may be a model for subclinical transmissible spongiform encephalopathy, since it protects mice from disease upon intraperitoneal administration of scrapie prions; however, a proportion of B-cell-deficient mice accumulate protease-resistant prion protein in their brains. Here, we have characterized this subclinical disease. In addition, we have studied the possibility that a neurotoxic factor secreted by B cells may contribute to pathogenesis. PMID:10516067

  10. Endocranial and masticatory muscle volumes in myostatin-deficient mice

    PubMed Central

    Jeffery, Nathan; Mendias, Christopher

    2014-01-01

    Structural and functional trade-offs are integral to the evolution of the mammalian skull and its development. This paper examines the potential for enlargement of the masticatory musculature to limit the size of the endocranial cavity by studying a myostatin-deficient mouse model of hypermuscularity (MSTN−/−). The study tests the null prediction that the larger MSTN−/− mice have larger brains compared with wild-type (WT) mice in order to service the larger muscles. Eleven post-mortem MSTN−/− mice and 12 WT mice were imaged at high resolution using contrast enhanced micro-CT. Masticatory muscle volumes (temporalis, masseter, internal and external pterygoids) and endocranial volumes were measured on the basis of two-dimensional manual tracings and the Cavalieri principle. Volumes were compared using Kruskal–Wallis and Student's t-tests. Results showed that the masticatory muscles of the MSTN−/− mice were significantly larger than in the WT mice. Increases were in the region of 17–36% depending on the muscle. Muscles increased in proportion to each other, maintaining percentages in the region of 5, 10, 21 and 62% of total muscle volume for the external ptyergoid, internal pterygoid, temporalis and masseter, respectively. Kruskal–Wallis and t-tests demonstrated that the endocranial volume was significantly larger in the WT mice, approximately 16% larger on average than that seen in the MSTN−/− mice. This comparative reduction of MSTN−/− endocranial size could not be explained in terms of observer bias, ageing, sexual dimorphism or body size scaling. That the results showed a reduction of brain size associated with an increase of muscle size falsifies the null prediction and lends tentative support to the view that the musculature influences brain growth. It remains to be determined whether the observed effect is primarily physical, nutritional, metabolic or molecular in nature. PMID:26064569

  11. Pair Housing Reverses Post-Stroke Depressive Behaviour in Mice

    PubMed Central

    Verma, Rajkumar; Friedler, Brett D.; Harris, Nia M.; McCullough, Louise D.

    2014-01-01

    Social isolation (SI) has been linked epidemiologically to high rates of morbidity and mortality following stroke. In contrast, strong social support enhances recovery and lowers stroke recurrence. However, the mechanism by which social support influences stroke recovery has not been adequately explored. The goal of this study was to examine the effect of post-stroke pair housing and SI on behavioural phenotypes and chronic functional recovery in mice. Young male mice were paired for 14 days before a 60 minute transient middle cerebral artery occlusion (MCAO) or sham surgery and assigned to various housing environments immediately after stroke. Post-stroke mice paired with either a sham or stroke partner showed significantly higher (p<0.05) sociability after MCAO than isolated littermates. Sociability deficits worsened over time in isolated animals. Pair-housed mice showed restored sucrose consumption (p<0.05) and reduced immobility in the tail suspension test compared to isolated cohorts. Pair-housed stroked mice demonstrated significantly reduced cerebral atrophy after 6 weeks (17.5 ± 1.5% in PH vs. 40.8 ± 1.3% in SI; p<0.001). Surprisingly, total brain arginase-1, a marker of a M2 “alternatively activated” myeloid cells was higher in isolated mice. However, a more detailed assessment of cellular expression showed a significant increase in the number of microglia that co-labeled with arginase-1 in the peri-infarct region in PH stroke mice compared to SI mice. Pair housing enhances sociability and reduces avolitional and anhedonic behaviour. Pair housing reduced serum IL-6 and enhanced peri-infarct microglia arginase-1 expression. Social interaction reduces post-stroke depression and improves functional recovery. PMID:24793492

  12. Chimeric Plantibody Passively Protects Mice against Aerosolized Ricin Challenge

    PubMed Central

    Sully, Erin K.; Whaley, Kevin J.; Bohorova, Natasha; Bohorov, Ognian; Goodman, Charles; Kim, Do H.; Pauly, Michael H.; Velasco, Jesus; Hiatt, Ernie; Morton, Josh; Swope, Kelsi; Roy, Chad J.; Zeitlin, Larry

    2014-01-01

    Recent incidents in the United States and abroad have heightened concerns about the use of ricin toxin as a bioterrorism agent. In this study, we produced, using a robust plant-based platform, four chimeric toxin-neutralizing monoclonal antibodies that were then evaluated for the ability to passively protect mice from a lethal-dose ricin challenge. The most effective antibody, c-PB10, was further evaluated in mice as a therapeutic following ricin exposure by injection and inhalation. PMID:24574537

  13. Antibiotic Administration in the Drinking Water of Mice

    PubMed Central

    Marx, James O; Vudathala, Daljit; Murphy, Lisa; Rankin, Shelley; Hankenson, F Claire

    2014-01-01

    Although antibiotics frequently are added to the drinking water of mice, this practice has not been tested to confirm that antibiotics reach therapeutic concentrations in the plasma of treated mice. In the current investigation, we 1) tested the stability of enrofloxacin and doxycycline in the drinking water of adult, female C57BL/6 mice; 2) measured the mice's consumption of water treated with enrofloxacin, doxycycline, amoxicillin, or trimethoprim–sulfamethoxazole; and 3) used HPLC to measure plasma antibiotic concentrations in mice that had ingested treated water for 1 wk. Plasma concentrations of antibiotic were measured 1 h after the start of both the light and dark cycle. The main findings of the study were that both enrofloxacin and nonpharmaceutical, chemical-grade doxycycline remained relatively stable in water for 1 wk. In addition, mice consumed similar volumes of antibiotic-treated and untreated water. The highest plasma antibiotic concentrations measured were: enrofloxacin, 140.1 ± 10.4 ng/mL; doxycycline, 56.6 ± 12.5 ng/mL; amoxicillin, 299.2 ± 64.1 ng/mL; and trimethoprim–sulfamethoxazole, 5.9 ± 1.2 ng/mL. Despite the stability of the antibiotics in the water and predictable water consumption by mice, the plasma antibiotic concentrations were well below the concentrations required for efficacy against bacterial pathogens, except for those pathogens that are exquisitely sensitive to the antibiotic. The findings of this investigation prompt questions regarding the rationale of the contemporary practice of adding antibiotics to the drinking water of mice for systemic antibacterial treatments. PMID:24827573

  14. Hexamita and Giardia as a cause of mortality in congenitally thymus-less (nude) mice

    PubMed Central

    Boorman, G. A.; Lina, P. H. C.; Zurcher, C.; Nieuwerkerk, H. T. M.

    1973-01-01

    Two intestinal flagellates, Hexamita muris and Giardia muris, were found in high concentrations in most of the congenitally thymus-less (nude) mice in a conventional colony being maintained at the Radiobiological Institute TNO. Antiflagellate therapy markedly reduced mortality, with >50% of the mice living to 110 days. In mice receiving thymus transplants but no antiflagellate treatment the mortality rate was less than in either control or treated mice. In addition, histopathological examination of mice with thymus transplants revealed fewer intestinal flagellates than in control mice. It is suggested that the wasting syndrome seen in nude and neonatally thymectomized mice may be aggravated by infestation with Hexamita and Giardia. PMID:4778720

  15. Progress on Superconducting Magnets for the MICE Cooling Channel

    SciTech Connect

    Green, Michael A; Virostek, Steve P.; Li, Derun; Zisman, Michael S.; Wang, Li; Pan, Heng; Wu, Hong; Guo, XingLong; Xu, FengYu; Liu, X. K.; Zheng, S. X.; Bradshaw, Thomas; Baynham, Elwyn; Cobb, John; Lau, Wing; Lau, Peter; Yang, Stephanie Q.

    2009-09-09

    The muon ionization cooling experiment (MICE) consists of a target, a beam line, a pion decay channel, the MICE cooling channel. Superconducting magnets are used in the pion decay channel and the MICE cooling channel. This report describes the MICE cooling channel magnets and the progress in the design and fabrication of these magnets. The MICE cooling channel consists of three types of superconducting solenoids; the spectrometer solenoids, the coupling solenoids and the focusing solenoids. The three types of magnets are being fabricated in he United States, China, and the United Kingdom respectively. The spectrometer magnets are used to analyze the muon beam before and after muon cooling. The coupling magnets couple the focusing sections and keep the muon beam contained within the iris of the RF cavities that re used to recover the muon momentum lost during ionization cooling. The focusing magnets focus the muon beam in the center of a liquid hydrogen absorber. The first of the cooling channel magnets will be operational in MICE in the spring of 2010.

  16. Host microbiota modulates development of social preference in mice

    PubMed Central

    Arentsen, Tim; Raith, Henrike; Qian, Yu; Forssberg, Hans; Heijtz, Rochellys Diaz

    2015-01-01

    Background Mounting evidence indicates that the indigenous gut microbiota exerts long-lasting programming effects on brain function and behaviour. Objective In this study, we used the germ-free (GF) mouse model, devoid of any microbiota throughout development, to assess the influence of the indigenous microbiota on social preference and repetitive behaviours (e.g. self-grooming). Methods and results Using the three-chambered social approach task, we demonstrate that when adult GF mice were given a choice to spend time with a novel mouse or object, they spent significantly more time sniffing and interacting with the stimulus mouse compared to conventionally raised mice (specific pathogen-free, SPF). Time spent in repetitive self-grooming behaviour, however, did not differ between GF and SPF mice. Real-time PCR–based gene expression analysis of the amygdala, a key region that is part of the social brain network, revealed a significant reduction in the mRNA levels of total brain-derived neurotrophic factor (BDNF), BDNF exon I-, IV-, VI-, IX-containing transcripts, and NGFI-A (a signalling molecule downstream of BDNF) in GF mice compared to SPF mice. Conclusion These results suggest that differential regulation of BDNF exon transcripts in the amygdala by the indigenous microbes may contribute to the altered social development of GF mice. PMID:26679775

  17. Knockout of Foxp2 disrupts vocal development in mice

    PubMed Central

    Castellucci, Gregg A.; McGinley, Matthew J.; McCormick, David A.

    2016-01-01

    The FOXP2 gene is important for the development of proper speech motor control in humans. However, the role of the gene in general vocal behavior in other mammals, including mice, is unclear. Here, we track the vocal development of Foxp2 heterozygous knockout (Foxp2+/−) mice and their wildtype (WT) littermates from juvenile to adult ages, and observe severe abnormalities in the courtship song of Foxp2+/− mice. In comparison to their WT littermates, Foxp2+/− mice vocalized less, produced shorter syllable sequences, and possessed an abnormal syllable inventory. In addition, Foxp2+/− song also exhibited irregular rhythmic structure, and its development did not follow the consistent trajectories observed in WT vocalizations. These results demonstrate that the Foxp2 gene is critical for normal vocal behavior in juvenile and adult mice, and that Foxp2 mutant mice may provide a tractable model system for the study of the gene’s role in general vocal motor control. PMID:26980647

  18. Electric field exposure and evidence of stress in mice

    SciTech Connect

    De Bruyn, L.; De Jager, L. )

    1994-04-01

    The effect of stress induced by an electric field on the adrenal gland cortex of mice was examined by means of corticosterone serum assay and evaluation of the lipid profile of the different zones of the cortex. Six generations of experimental mice were exposed to a 10 kV/m electric field from conception and corresponding control groups were sham exposed. Mice were sacrificed at 35 days (n = 10), as adults (n = 20) and at 18 months (old mice) (n = 10). Blinded lipid estimates were performed on histological preparations of the adrenals, serum corticosterone levels were determined, and the results were statistically analyzed. The mean lipid volume in the zona glomerulosa of the exposed adult male group was significantly higher than that of the control group (P = 0.004). The median daytime corticosterone level of the exposed male mice was also significantly higher than that in the controls (P = 0.02). The lipid profiles and corticosterone values in the other subgroups did not differ significantly. As chronic stress increases the lipid volume of all the zones of the adrenal cortex and stimulates the zona glomerulosa to corticosterone secretion, the data suggest that the electric field acted as a chronic stressor in the adult male mice. 21 refs., 6 figs., 2 tabs.

  19. Early amyloid accumulation in the hippocampus of SAMP8 mice.

    PubMed

    Del Valle, Jaume; Duran-Vilaregut, Joaquim; Manich, Gemma; Casadesús, Gemma; Smith, Mark A; Camins, Antoni; Pallàs, Mercè; Pelegrí, Carme; Vilaplana, Jordi

    2010-01-01

    Late-onset Alzheimer's disease (AD) is the most common form of AD appearing after 65 years of age. To date, however, there are no non-genetically manipulated rodent models that develop a similar sporadic onset of AD with age-related amyloid-beta (Abeta) deposition. Although the senescence accelerated mouse prone 8 (SAMP8) mice have been proposed as a model of AD, the presence of Abeta deposits remains controversial. In this study, we describe the time course of Abeta deposition in SAMP8 mice as well as in control SAMR1 and ICR-CD1 strains of mice. From as early as 6 months onward, SAMP8 mice show Abeta deposition in the hippocampus that increase in number and extent with age. These deposits are comprised of by clustered granules that contain Abeta{42}, Abeta{40}, and other Abeta protein precursor fragments. By marked contrast, control mice show only low numbers of Abeta clusters that do not develop until 15 months of age. The demonstration that SAMP8 mice present with amyloid deposits in their hippocampus makes this animal model a useful tool to understand the mechanisms involved in Abeta deposition in AD. PMID:20061609

  20. [BEHAVIOR, MEMORY AND IMMUNOLOGICAL STATUS IN MICE MODEL OF DESYNCHRONOSIS].

    PubMed

    Dubrovina, N I; Shurlygina, A V; Litvinenko, G I; Melnikova, E V; Tenditnik, M V; Chasovskich, M I; Trufakin, V A

    2015-05-01

    Interstrain differences in behavior and parameters of the immune system of CBA and C57BL/6 mice with round the clock coverage (KO) were investigated. Open field, light/dark, acoustic startle response, forced swimming, elevated plus-maze, passive avoidance were used for measuring emotional behavior and memory. The number of lymphocyte subpopulations CD3+, CD4+8-, CD4-8+, CD4+8+, CD19+, CD3+hi spleen and thymus, the ratio of cells in different phases of the cell cycle was determined by flow cytometry. C57BL/6J mice strictly increased anxiety in response to the KO compared to CBA mice. Moreover, KO-treated C57BL/6J mice impaired the passive avoidance learning. We found that KO evoked significant changes in the cellular composition of the thymus and decrease of thymocytes proliferation in C57BL/6J mice. In opposite KO-treated CBA mice showed change of splenic cellular structure with increased % CD19+ cells and the proliferation of splenocytes. Our study demonstrated genotype-dependent reactions of the nervous and immune systems in response chronic constant light. PMID:26263684

  1. Studies of an expanded trinucleotide repeat in transgenic mice

    SciTech Connect

    Bingham, P.; Wang, S.; Merry, D.

    1994-09-01

    Spinal and bulbar muscular atrophy (SBMA) is a progressive motor neuron disease caused by expansion of a trinucleotide repeat in the androgen receptor gene (AR{sup exp}). AR{sup exp} repeats expand further or contract in approximately 25% of transmissions. Analogous {open_quotes}dynamic mutations{close_quotes} have been reported in other expanded trinucleotide repeat disorders. We have been developing a mouse model of this disease using a transgenic approach. Expression of the SBMA AR was documented in transgenic mice with an inducible promoter. No phenotypic effects of transgene expression were observed. We have extended our previous results on stability of the expanded trinucleotide repeat in transgenic mice in two lines carrying AR{sup exp}. Tail DNA was amplified by PCR using primers spanning the repeat on 60 AR{sup exp} transgenic mice from four different transgenic lines. Migration of the PCR product through an acrylamide gel showed no change of the 45 CAG repeat length in any progeny. Similarly, PCR products from 23 normal repeat transgenics showed no change from the repeat length of the original construct. Unlike the disease allele in humans, the expanded repeat AR cDNA in transgenic mice showed no change in repeat length with transmission. The relative stability of CAG repeats seen in the transgenic mice may indicate either differences in the fidelity of replicative enzymes, or differences in error identification and repair between mice and humans. Integration site or structural properties of the transgene itself might also play a role.

  2. Norepinephrine Transporter Heterozygous Knockout Mice Exhibit Altered Transport and Behavior

    PubMed Central

    Fentress, HM; Klar, R; Krueger, JK; Sabb, T; Redmon, SN; Wallace, NM; Shirey-Rice, JK; Hahn, MK

    2013-01-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically-driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET+/−), demonstrating that they display an ~50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity, assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET+/− mouse establishes an activated state of existing, surface NET proteins. NET+/− mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris Water Maze. These data suggest recovery of near basal activity in NET+/− mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET+/− mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders. PMID:24102798

  3. Stevia and Saccharin Preferences in Rats and Mice

    PubMed Central

    Bahrani, Mahsa; Zukerman, Steven; Ackroff, Karen

    2010-01-01

    Use of natural noncaloric sweeteners in commercial foods and beverages has expanded recently to include compounds from the plant Stevia rebaudiana. Little is known about the responses of rodents, the animal models for many studies of taste systems and food intake, to stevia sweeteners. In the present experiments, preferences of female Sprague–Dawley rats and C57BL/6J mice for different stevia products were compared with those for the artificial sweetener saccharin. The stevia component rebaudioside A has the most sweetness and least off-tastes to human raters. In ascending concentration tests (48-h sweetener vs. water), rats and mice preferred a high-rebaudioside, low-stevioside extract as strongly as saccharin, but the extract stimulated less overdrinking and was much less preferred to saccharin in direct choice tests. Relative to the extract, mice drank more pure rebaudioside A and showed stronger preferences but still less than those for saccharin. Mice also preferred a commercial mixture of rebaudioside A and erythritol (Truvia). Similar tests of sweet receptor T1R3 knockout mice and brief-access licking tests with normal mice suggested that the preferences were based on sweet taste rather than post-oral effects. The preference response of rodents to stevia sweeteners is notable in view of their minimal response to some other noncaloric sweeteners (aspartame and cyclamate). PMID:20413452

  4. Quercetin vs chrysin: effect on liver histopathology in diabetic mice.

    PubMed

    Sirovina, D; Orsolić, N; Koncić, M Z; Kovacević, G; Benković, V; Gregorović, G

    2013-10-01

    Effects of flavonoids quercetin and chrysin on lipid peroxidation and histopathological changes in liver of diabetic mice were studied and compared with the antioxidant and reducing ability of quercetin and chrysin and their ability to chelate Fe(2+) ions in vitro. Diabetes was induced in Swiss albino mice with a single intravenous injection of alloxan (75 mg kg(-1)). Two days after alloxan injection, flavonoid preparations (50 mg kg(-1) per day) were given intraperitoneally for 7 days in diabetic mice. The lipid peroxidation was evaluated by measuring the malondialdehyde production using the 2-thiobarbituric acid test. Administration of quercetin and chrysin to diabetic mice resulted in a significant decrease in lipid peroxidation level in liver tissue. Treatment of diabetic mice with flavonoids solutions results in decreased number of vacuolated cells and degree of vacuolization of the liver tissue. The protective role of flavonoids against the reactive oxygen species-induced damages in diabetic mice gives a hope that they may exert similar protective action in humans. PMID:23357962

  5. Increased alcohol consumption in relaxin-3 deficient male mice.

    PubMed

    Shirahase, Takahira; Aoki, Miku; Watanabe, Ryuji; Watanabe, Yoshihisa; Tanaka, Masaki

    2016-01-26

    Relaxin-3 is a neuropeptide expressed in the brainstem, and predominantly localized in the gray matter of the midline dorsal pons termed the nucleus incertus. Relaxin-3-expressing neurons densely project axons rostrally to various forebrain regions including the septum, hippocampus, and lateral hypothalamus. Several relaxin-3 functions have been reported including food intake, stress responses, neuroendocrine function, emotion, and spatial memory. In addition, recently relaxin-3 and its receptor, RXFP3, were shown to regulate alcohol intake using an RXFP3 antagonist and RXFP3 gene knockout mice. In the present study, we investigated alcohol consumption in relaxin-3 knockout mice, and found that male but not female mice significantly drank more alcohol than wild-type mice in the two-bottle choice test. However, after chronic alcohol vapor exposure, wild-type and mutant mice did not show this difference in alcohol intake, although both genotypes exhibited increased alcohol consumption compared with non-alcohol-exposed control mice. There was no genotype difference in sucrose or quinine preference. These results suggest that the relaxin-3 neuronal system modestly affects alcohol preference and consumption. PMID:26687275

  6. Fish oil concentrate delays sensitivity to thermal nociception in mice

    PubMed Central

    Veigas, Jyothi M.; Williams, Paul J.; Halade, Ganesh; Rahman, Mizanur M.; Yoneda, Toshiyuki; Fernandes, Gabriel

    2011-01-01

    Fish oil has been used to alleviate pain associated with inflammatory conditions such as rheumatoid arthritis. The anti-inflammatory property of fish oil is attributed to the n-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid. Contrarily, vegetable oils such as safflower oil are rich in n-6 fatty acids which are considered to be mediators of inflammation. This study investigates the effect of n-3 and n-6 fatty acids rich oils as dietary supplements on the thermally induced pain sensitivity in healthy mice. C57Bl/6J mice were fed diet containing regular fish oil, concentrated fish oil formulation (CFO) and safflower oil (SO) for 6 months. Pain sensitivity was measured by plantar test and was correlated to the expression of acid sensing ion channels (ASICs), transient receptor potential vanilloid 1 (TRPV1) and c-fos in dorsal root ganglion cells. Significant delay in sensitivity to thermal nociception was observed in mice fed CFO compared to mice fed SO (p<0.05). A significant diminution in expression of ion channels such as ASIC1a (64%), ASIC13 (37%) and TRPV1 (56%) coupled with reduced expression of c-fos, a marker of neuronal activation, was observed in the dorsal root ganglion cells of mice fed CFO compared to that fed SO. In conclusion, we describe here the potential of fish oil supplement in reducing sensitivity to thermal nociception in normal mice. PMID:21345372

  7. Norepinephrine transporter heterozygous knockout mice exhibit altered transport and behavior.

    PubMed

    Fentress, H M; Klar, R; Krueger, J J; Sabb, T; Redmon, S N; Wallace, N M; Shirey-Rice, J K; Hahn, M K

    2013-11-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET(+/-) ), demonstrating that they display an approximately 50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET(+/-) mouse establishes an activated state of existing surface NET proteins. The NET(+/-) mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris water maze. These data suggest that recovery of near basal activity in NET(+/-) mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET(+/-) mice represent a unique model t