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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. 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

  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 Central

    Lee, Bai-Yu; Horwitz, Marcus A.

    2012-01-01

    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. Impact of donor MHC class I or class II antigen deficiency on first- and second-set rejection of mouse heart or liver allografts.

    PubMed Central

    Qian, S; Fu, F; Li, Y; Lu, L; Rao, A S; Starzl, T E; Thomson, A W; Fung, J J

    1996-01-01

    The influence of donor major histocompatibility complex (MHC) class I- or class II-deficiency on the initiation of first- and second-set rejection of mouse heart and liver allografts was examined. C3H (H-2k) mice received heterotopic cardiac or orthotopic liver grafts from unmodified B10 (H-2b), B6 (H-2b), b2m (H-2b; class I deficient) or AB0 (H-2b; class II deficient) donors. Organ survival was also investigated in C3H recipients that had been presensitized by a normal B10 skin graft 2-3 weeks before heart or liver transplantation. The absence of cell surface MHC class I or class II resulted in significant prolongation of primary cardiac allograft survival. Three of seven (43%) MHC class I-deficient, and two of five (40%) class II-deficient heart grafts were accepted indefinitely (survival time > 100 days). Thus both MHC class I and class II molecules appear to be important for the elicitation of first-set rejection in the heart allograft model. All liver allografts survived > 100 days in normal recipients. In C3H recipients that had been presensitized by a B10 skin graft, however, both heart and liver grafts from AB0 (class II deficient) donors underwent accelerated rejection (median survival time [MST] 3 and 4 days, respectively). In contrast, liver grafts from class I-deficient mice (b2m) were still accepted indefinitely by B10 skin-presensitized C3H recipients, whereas class I-deficient hearts survived significantly longer than those from class II-deficient or normal donors. These data demonstrate that the expression of donor MHC class I, and not class II is crucial in initiating second-set organ allograft rejection. In vitro monitoring revealed that at the time of organ transplant, both splenocytes and serum of the skin-presensitized animals displayed high cytotoxicity against AB0 (class II-deficient) but not against b2m (class I-deficient) targets. PMID:8707337

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Grace period. 136a.33 Section 136a.33 Public Health... HEALTH AND HUMAN SERVICES INDIAN HEALTH Transition Provisions 136a.33 Grace period. (a) Upon the... of the new eligibility regulations) shall retain their eligibility for a six month grace...

  6. 42 CFR 136a.33 - Grace period.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Grace period. 136a.33 Section 136a.33 Public Health... HEALTH AND HUMAN SERVICES INDIAN HEALTH Transition Provisions 136a.33 Grace period. (a) Upon the... of the new eligibility regulations) shall retain their eligibility for a six month grace...

  7. 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... HEALTH AND HUMAN SERVICES INDIAN HEALTH Transition Provisions 136a.33 Grace period. (a) Upon the... of the new eligibility regulations) shall retain their eligibility for a six month grace...

  8. 42 CFR 136a.33 - Grace period.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Grace period. 136a.33 Section 136a.33 Public Health... HEALTH AND HUMAN SERVICES INDIAN HEALTH Transition Provisions 136a.33 Grace period. (a) Upon the... of the new eligibility regulations) shall retain their eligibility for a six month grace...

  9. 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... HEALTH AND HUMAN SERVICES INDIAN HEALTH Transition Provisions 136a.33 Grace period. (a) Upon the... of the new eligibility regulations) shall retain their eligibility for a six month grace...

  10. Preparation and preclinical evaluation of humanised A33 immunoconjugates for radioimmunotherapy.

    PubMed Central

    King, D. J.; Antoniw, P.; Owens, R. J.; Adair, J. R.; Haines, A. M.; Farnsworth, A. P.; Finney, H.; Lawson, A. D.; Lyons, A.; Baker, T. S.

    1995-01-01

    A humanised IgG1/k version of A33 (hA33) has been constructed and expressed with yields up to 700 mg l-1 in mouse myeloma NS0 cells in suspension culture. The equilibrium dissociation constant of hA33 (KD = 1.3 nM) was shown to be equivalent to that of the murine antibody in a cell-binding assay. hA33 labelled with yttrium-90 using the macrocyclic chelator 12N4 (DOTA) was shown to localise very effectively to human colon tumour xenografts in nude mice, with tumour levels increasing as blood concentration fell up to 144 h. A Fab' variant of hA33 with a single hinge thiol group to facilitate chemical cross-linking has also been constructed and expressed with yields of 500 mg l-1. Trimaleimide cross-linkers have been used to produce a trivalent Fab fragment (hA33 TFM) that binds antigen on tumour cells with greater avidity than hA33 IgG. Cross-linkers incorporating 12N4 or 9N3 macrocycles have been used to produce hA33 TFM labelled stably and site specifically with yttrium-90 or indium-111 respectively. These molecules have been used to demonstrate that hA33 TFM is cleared more rapidly than hA33 IgG from the circulation of animals but does not lead to accumulation of these metallic radionuclides in the kidney. 90Y-labelled hA33 TFM therefore appears to be the optimal form of the antibody for radioimmunotherapy of colorectal carcinoma. Images Figure 3 PMID:8519646

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

    PubMed

    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

    2015-09-01

    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

  12. 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

  13. 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...

  14. 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...

  15. 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...

  16. O-Antigen-Negative Salmonella enterica Serovar Typhimurium Is Attenuated in Intestinal Colonization but Elicits Colitis in Streptomycin-Treated Mice?

    PubMed Central

    Ilg, Karin; Endt, Kathrin; Misselwitz, Benjamin; Stecher, Brbel; Aebi, Markus; Hardt, Wolf-Dietrich

    2009-01-01

    Lipopolysaccharide (LPS) is a major constituent of the outer membrane and an important virulence factor of Salmonella enterica subspecies 1 serovar Typhimurium (serovar Typhimurium). To evaluate the role of LPS in eliciting intestinal inflammation in streptomycin-treated mice, we constructed an O-antigen-deficient serovar Typhimurium strain through deletion of the wbaP gene. The resulting strain was highly susceptible to human complement activity and the antimicrobial peptide mimic polymyxin B. Furthermore, it showed a severe defect in motility and an attenuated phenotype in a competitive mouse infection experiment, where the ?wbaP strain (SKI12) was directly compared to wild-type Salmonella. Nevertheless, the ?wbaP strain (SKI12) efficiently invaded HeLa cells in vitro and elicited acute intestinal inflammation in streptomycin-pretreated mice. Our experiments prove that the presence of complete LPS is not essential for in vitro invasion or for triggering acute colitis. PMID:19364844

  17. 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

  18. 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

  19. Suppression of cytokines in mice by protein A-V antigen fusion peptide and restoration of synthesis by active immunization.

    PubMed

    Nakajima, R; Motin, V L; Brubaker, R R

    1995-08-01

    It is established that an approximately 70-kb Lcr plasmid enables Yersinia pestis, the causative agent of bubonic plague, to multiply in focal necrotic lesions within visceral organs of mice by preventing net synthesis of the cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), thereby minimizing inflammation (Lcr+). Rabbit antiserum raised against cloned staphylococcal protein A-V antigen fusion peptide (PAV) is known to passively immunize mice against 10 minimum lethal doses of intravenously injected Lcr+ cells of Y. pestis. In this study, injected PAV suppressed TNF-alpha and IFN-gamma in mice challenged with avirulent V antigen-deficient Y. pestis (lcrV or Lcr-) and promoted survival in vivo of these isolates as well as salmonellae and Listeria monocytogenes (with which the outcome was lethal). Active immunization of mice with PAV protected against 1,000 minimum lethal doses of intravenously injected Lcr+ cells of Y. pestis and Yersinia pseudotuberculosis but not Yersinia enterocolitica. The progressive necrosis provoked by Lcr+ cells of Y. pestis in visceral organs of nonimmunized mice was replaced after active immunization with PAV by massive infiltration of neutrophils and mononuclear cells (which generated protective granulomas indistinguishable from those formed against avirulent Lcr- mutants in nonimmunized mice). Distinct multiple abscesses typical of Lcr+ cells of Y. pseudotuberculosis were prevented by similar immunization. Significant synthesis of TNF-alpha and IFN-gamma occurred in spleens of mice actively immunized with PAV after challenge with Lcr+ cells of Y. pestis. These findings suggest that V antigen contributes to disease by suppressing the normal inflammatory response. PMID:7622225

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

    PubMed

    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

    2015-08-01

    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

  1. 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

  2. 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.

  3. A 33-year-old man with multiple bilateral pulmonary pseudoaneurysms.

    PubMed

    Rokadia, Haala K; Heresi, Gustavo A; Tan, Carmela D; Raymond, Daniel P; Budd, George Thomas; Farver, Carol

    2015-10-01

    A 33-year-old man, never smoker, presented with acute-onset dyspnea secondary to bilateral pulmonary emboli. Echocardiography at the time revealed a right atrial myxoma, for which he underwent resection, followed by anticipated lifelong therapeutic anticoagulation therapy. PMID:26437818

  4. 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.

  5. Delayed Cardiomyopathy in Dystrophin Deficient mdx Mice Relies on Intrinsic Glutathione Resource

    PubMed Central

    Khouzami, Lara; Bourin, Marie-Claude; Christov, Christo; Damy, Thibaud; Escoubet, Brigitte; Caramelle, Philippe; Perier, Magali; Wahbi, Karim; Meune, Christophe; Pavoine, Catherine; Pecker, Franoise

    2010-01-01

    Oxidative stress contributes to the pathogenesis of Duchenne muscular dystrophy (DMD). Although they have been a model for DMD, mdx mice exhibit slowly developing cardiomyopathy. We hypothesized that disease process was delayed owing to the development of an adaptive mechanism against oxidative stress, involving glutathione synthesis. At 15 to 20 weeks of age, mdx mice displayed a 33% increase in blood glutathione levels compared with age-matched C57BL/6 mice. In contrast, cardiac glutathione content was similar in mdx and C57BL/6 mice as a result of the balanced increased expression of glutamate cysteine ligase catalytic and regulatory subunits ensuring glutathione synthesis in the mdx mouse heart, as well as increased glutathione peroxidase-1 using glutathione. Oral administration from 10 weeks of age of the glutamate cysteine ligase inhibitor, l-buthionine(S,R)-sulfoximine (BSO, 5 mmol/L), led to a 33% and 50% drop in blood and cardiac glutathione, respectively, in 15- to 20-week-old mdx mice. Moreover, 20-week-old BSO-treated mdx mice displayed left ventricular hypertrophy associated with diastolic dysfunction, discontinuities in ?-dystroglycan expression, micronecrosis and microangiopathic injuries. Examination of the glutathione status in four DMD patients showed that three displayed systemic glutathione deficiency as well. In conclusion, low glutathione resource hastens the onset of cardiomyopathy linked to a defect in dystrophin in mdx mice. This is relevant to the glutathione deficiency that DMD patients may suffer. PMID:20696779

  6. Newly Emerging Feeding Difficulties in a 33-Year-Old Adult With CHARGE Syndrome.

    PubMed

    Hudson, Alexandra; Blake, Kim

    2016-01-01

    Feeding and swallowing difficulties are common among individuals with CHARGE syndrome. Many children require gastrostomy tube feeding in their early years and often undergo a delay in feeding and oral-motor skill development. There is little information available on adults with CHARGE syndrome, and the feeding difficulties they face. The present case describes newly emerging mouth over-stuffing feeding behaviors and feeding difficulties in a 33-year-old adult with CHARGE syndrome who had not undergone feeding therapy since childhood. PMID:26668685

  7. Characterization of the ars Gene Cluster from Extremely Arsenic-Resistant Microbacterium sp. Strain A33?

    PubMed Central

    Achour-Rokbani, Asma; Cordi, Audrey; Poupin, Pascal; Bauda, Pascale; Billard, Patrick

    2010-01-01

    The arsenic resistance gene cluster of Microbacterium sp. A33 contains a novel pair of genes (arsTX) encoding a thioredoxin system that are cotranscribed with an unusual arsRC2 fusion gene, ACR3, and arsC1 in an operon divergent from arsC3. The whole ars gene cluster is required to complement an Escherichia coli ars mutant. ArsRC2 negatively regulates the expression of the pentacistronic operon. ArsC1 and ArsC3 are related to thioredoxin-dependent arsenate reductases; however, ArsC3 lacks the two distal catalytic cysteine residues of this class of enzymes. PMID:19966021

  8. Newly Emerging Feeding Difficulties in a 33-Year-Old Adult With CHARGE Syndrome

    PubMed Central

    Hudson, Alexandra; Blake, Kim

    2016-01-01

    Feeding and swallowing difficulties are common among individuals with CHARGE syndrome. Many children require gastrostomy tube feeding in their early years and often undergo a delay in feeding and oral-motor skill development. There is little information available on adults with CHARGE syndrome, and the feeding difficulties they face. The present case describes newly emerging mouth over-stuffing feeding behaviors and feeding difficulties in a 33-year-old adult with CHARGE syndrome who had not undergone feeding therapy since childhood. PMID:26668685

  9. 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

  10. Estrogen Receptor-? Knockout Mice.

    PubMed

    Antonson, Per; Humire, Patricia; Gustafsson, Jan-ke

    2016-01-01

    Tissue specific knockout mice are valuable tools to study gene function in vivo. The method uses the Cre/loxP system in which loxP sites are cloned into the genome surrounding one or more exons of a gene and the targeted exon(s) are deleted when the Cre enzyme is expressed. Mouse lines that are prepared for the generation of knockout ER? mice have been developed independently by many research groups and the number of available transgenic mouse lines that express Cre under tissue specific promoters is large. Here, we describe how tissue specific ER? knockout mice are generated. PMID:26585154

  11. A 33-month-old with fever and altered mental status.

    PubMed

    Lautz, Andrew J; Jenssen, Brian; McGuire, Jennifer; St Geme, Joseph W

    2015-01-01

    A 33-month-old girl presented with 3 days of fever and 1 day of multiple paroxysmal episodes of screaming with apparent unresponsiveness, flexed lower extremities, clenched hands, and upward eye deviation. These events lasted seconds to a minute at a time and occurred only during sleep. She slept peacefully between episodes and was easily awakened. She had a history of mild speech delay and mild intermittent asthma but was otherwise healthy. She was tired-appearing and fussy on examination with dry mucous membranes, but her examination was otherwise normal. A complete blood count with differential and serum levels of sodium, potassium, chloride, and calcium were normal, but her bicarbonate level was 12 mmol/L. Her fingerstick glucose level was 69 mg/dL. Urine dipstick was notable for large ketones, and a urine drug screen was normal. Cerebrospinal fluid examination yielded 2 white blood cells and 1040 red blood cells/mm(3) with normal chemistries. A computed tomography (CT) scan of her head was unremarkable, and an abdominal ultrasound demonstrated no evidence of intussusception. Over the course of her hospitalization, these paroxysmal episodes persisted, and she subsequently developed mutism, right-sided weakness, and difficulty swallowing liquids. Here we present her case, diagnostic evaluation, and ultimate diagnosis. PMID:25489012

  12. 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

  13. 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 havent 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

  14. 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

  15. 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…

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Single-chip color imaging for UHDTV camera with a 33M-pixel CMOS image sensor

    NASA Astrophysics Data System (ADS)

    Funatsu, Ryohei; Yamashita, Takayuki; Mitani, Kohji; Nojiri, Yuji

    2011-03-01

    To develop an ultrahigh-definition television (UHDTV) camera-with a resolution 16 times higher than that of HDTV resolution and a frame rate of 60 Hz (progressive)-a compact and high-mobility UHDTV camera using a 33M-pixel CMOS image sensor to provide single-chip color imaging was developed. The sensor has a Bayer color-filter array (CFA), and its output signal format is compatible with the conventional UHDTV camera that uses four 8M-pixel image sensors. The theoretical MTF characteristics of the single-chip camera and a conventional four-8M-pixel CMOS camera were first calculated. A new technique for Bayer CFA demosaicing used for the single-chip UHDTV camera was then evaluated. Finally, a pick-up system for single-chip imaging with a 33M-pixel color CMOS image sensor was measured. The measurement results show that the resolution of this is equivalent to or surpasses that of the conventional four-8M-pixel CMOS camera. The possibility of a practical compact UHDTV camera that makes use of single-chip color imaging was thereby confirmed.

  5. Grid cells in mice.

    PubMed

    Fyhn, Marianne; Hafting, Torkel; Witter, Menno P; Moser, Edvard I; Moser, May-Britt

    2008-01-01

    The medial entorhinal cortex (EC) is a part of the neural network for the representation of self-location in the rat. The key cell type of this system is the grid cell, whose multiple firing fields span the environment in a remarkably regular triangular or hexagonal pattern. The basic properties of grid cells and other cell types have been described, but the neuronal mechanisms responsible for the formation and maintenance of the place code remain elusive. These mechanisms can be investigated by genetic intervention strategies, where specific components of the entorhinal-hippocampal network are activated or silenced. Because of the common use of knockout mice for such targeted interventions, we asked if grid activity is expressed also in the mouse. Principal neurons in the superficial layers of mouse medial EC had stable grid fields similar to those of the rat. Neighboring grid cells shared a common spacing and orientation but had a different spatial phase, such that a small number of grid cells collectively represented all locations in the environment. The spacing of the grid increased with distance from the dorsal border of the medial EC. The lowest values for grid spacing, recorded at the dorsal end, were comparable to those of the rat, suggesting that grid fields do not scale up proportionally with body size. Grid cells were colocalized with head-direction cells and conjunctive place x head-direction cells, as in the rat. The demonstration of grid cells in mice prepares the ground for transgenic analyses of the entorhinal-hippocampal network. PMID:18683845

  6. 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

  7. 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.

  8. 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.

  9. Owls and larks in mice.

    PubMed

    Pfeffer, Martina; Wicht, Helmut; von Gall, Charlotte; Korf, Horst-Werner

    2015-01-01

    Humans come in different chronotypes and, particularly, the late chronotype (the so-called owl) has been shown to be associated with several health risks. A number of studies show that laboratory mice also display various chronotypes. In mice as well as in humans, the chronotype shows correlations with the period length and rhythm stability. In addition, some mouse models for human diseases show alterations in their chronotypic behavior, which are comparable to those humans. Thus, analysis of the behavior of mice is a powerful tool to unravel the molecular and genetic background of the chronotype and the prevalence of risks and diseases that are associated with it. In this review, we summarize the correlation of chronotype with free-running period length and rhythm stability in inbred mouse strains, in mice with a compromised molecular clockwork, and in a mouse model for neurodegeneration. PMID:26029157

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Acute Starvation Protects Mice Against Listeria monocytogenes

    PubMed Central

    Wing, Edward J.; Young, James B.

    1980-01-01

    We investigated the effect of starvation on the course of Listeria monocytogenes infections in mice. Mice starved for 24, 48, or 72 h and then inoculated with a lethal dose of L. monocytogenes showed significantly less mortality than mice not starved (i.e., fed mice). The protective effect of 48 or 72 h of starvation began immediately after the starvation period and persisted for at least 48 h. Starved, infected mice had significantly fewer L. monocytogenes cells in their spleens 2, 3, and 4 days after infection than did fed mice. Neither changes in T-lymphocyte function nor serum factors appeared to be responsible for the protective effect. Delayed hypersensitivity responses to L. monocytogenes antigen were smaller in starved mice than in fed mice. Adoptive transfer of spleen cells from nonimmune starved mice did not protect against L. monocytogenes. Additional studies indicated that the serum of starved mice did not inhibit multiplication of L. monocytogenes in vitro, nor was it able to transfer protection against L. monocytogenes to normal mice. In contrast, peritoneal macrophages from starved mice inhibited deoxyribonucleic acid synthesis of P815 tumor cells compared with macrophages from control mice. Therefore, the resistance of starved mice to L. monocytogenes is most likely due to nonspecific factors, one of which may be activation of macrophages. PMID:6772566

  18. 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

  19. Carotid chemoreceptor development in mice.

    PubMed

    Shirahata, Machiko; Kostuk, Eric W; Pichard, Luis E

    2013-01-01

    Mice are the most suitable species for understanding genetic aspects of postnatal developments of the carotid body due to the availability of many inbred strains and knockout mice. Our study has shown that the carotid body grows differentially in different mouse strains, indicating the involvement of genes. However, the small size hampers investigating functional development of the carotid body. Hypoxic and/or hyperoxic ventilatory responses have been investigated in newborn mice, but these responses are indirect assessment of the carotid body function. Therefore, we need to develop techniques of measuring carotid chemoreceptor neural activity from young mice. Many studies have taken advantage of the knockout mice to understand chemoreceptor function of the carotid body, but they are not always suitable for addressing postnatal development of the carotid body due to lethality during perinatal periods. Various inbred strains with well-designed experiments will provide useful information regarding genetic mechanisms of the postnatal carotid chemoreceptor development. Also, targeted gene deletion is a critical approach. PMID:22634368

  20. Practical pathology of aging mice

    PubMed Central

    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

  1. Carotid chemoreceptor development in mice

    PubMed Central

    Shirahata, Machiko; Kostuk, Eric W; Pichard, Luis E

    2012-01-01

    Mice are the most suitable species for understanding genetic aspects of postnatal developments of the carotid body due to the availability of many inbred strains and knockout mice. Our study has shown that the carotid body grows differentially in different mouse strains, indicating the involvement of genes. However, the small size hampers investigating functional development of the carotid body. Hypoxic and/or hyperoxic ventilatory responses have been investigated in newborn mice, but these responses are indirect assessment of the carotid body function. Therefore, we need to develop techniques of measuring carotid chemoreceptor neural activity from young mice. Many studies have taken advantage of the knockout mice to understand chemoreceptor function of the carotid body, but they are not always suitable for addressing postnatal development of the carotid body due to lethality during perinatal periods. Various inbred strains with well-designed experiments will provide useful information regarding genetic mechanisms of the postnatal carotid chemoreceptor development. Also, targeted gene deletion is a critical approach. PMID:22634368

  2. 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

  3. 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

  4. 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.

  5. Ambulatory ECG Recording in Mice

    PubMed Central

    McCauley, Mark D.; Wehrens, Xander H.T

    2010-01-01

    Telemetric ECG recording in mice is essential to understanding the mechanisms behind arrhythmias, conduction disorders, and sudden cardiac death. Although the surface ECG is utilized for short-term measurements of waveform intervals, it is not practical for long-term studies of heart rate variability or the capture of rare episodes of arrhythmias. Implantable ECG telemeters offer the advantages of simple surgical implantation, long-term recording of electrograms in ambulatory mice, and scalability with simultaneous recordings of multiple animals. Here, we present a step-by-step guide to the implantation of telemeters for ambulatory ECG recording in mice. Careful adherence to aseptic technique is required for favorable survival results with the possibility of implantation and recording from weeks to months. Thus, implantable ECG telemetry is a valuable tool for detection of critical information on cardiac electrophysiology in ambulatory animal models such as the mouse. PMID:20517202

  6. 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

  7. 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

  8. 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

  9. Ultrasonic Songs of Male Mice

    PubMed Central

    2005-01-01

    Previously it was shown that male mice, when they encounter female mice or their pheromones, emit ultrasonic vocalizations with frequencies ranging over 30110 kHz. Here, we show that these vocalizations have the characteristics of song, consisting of several different syllable types, whose temporal sequencing includes the utterance of repeated phrases. Individual males produce songs with characteristic syllabic and temporal structure. This study provides a quantitative initial description of male mouse songs, and opens the possibility of studying song production and perception in an established genetic model organism. PMID:16248680

  10. 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.

  11. Mitochondrial DNA Evolution in Mice

    PubMed Central

    Ferris, Stephen D.; Sage, Richard D.; Prager, Ellen M.; Ritte, Uzi; Wilson, Allan C.

    1983-01-01

    This study extends knowledge of mitochondrial DNA (mtDNA) diversity in mice to include 208 animals belonging to eight species in the subgenus Mus. Highly purified mtDNA from each has been subjected to high-resolution restriction mapping with respect to the known sequence of one mouse mtDNA. Variation attributed to base substitutions was encountered at about 200 of the 300 cleavage sites examined, and a length mutation was located in or near the displacement loop. The variability of different functional regions in this genome was as follows, from least to most: ribosomal RNA, transfer RNA, known proteins, displacement loop and unidentified reading frames.Phylogenetic analysis confirmed the utility of the Sage and Marshall revision of mouse classification, according to which there are at least four species of commensal mice and three species of aboriginal mice in the complex that was formerly considered to be one species. The most thoroughly studied of these species is Mus domesticus, the house mouse of Western Europe and the Mediterranean region, which is the mitochondrial source of all 50 of the laboratory strains examined and of the representatives of wild house mice introduced by Europeans to North and South America during the past few hundred years.The level of mtDNA variation among wild representatives of (M. musculus) and several other mammalian species. By contrast, among the many laboratory strains that are known or suspected to stem from the pet mouse trade, there is little interstrain variation, most strains having the "old inbred" type of domesticus mtDNA, whose frequency in the 145 wild mice examined is low, about 0.04. Also notable is the apparent homogeneity of mtDNA in domesticus races that have fixed six or more fused chromosomes and the close relationship of some of these mtDNAs to those of karyotypically normal mice.In addition, this paper discusses fossil and other evidence for the view that in mice, as in many other mammals, the average rate of point mutational divergence in mtDNA is 24% per million years. From this, it is estimated that the commensal association between mice and our ancestors began more than a million years ago, i.e., at an early stage in the evolution of Homo erectus. PMID:6315529

  12. COMPARATIVE TOXICITY OF AZINPHOS-METHYL TO HOUSE MICE, LABORATORY MICE, DEER MICE, AND GRAY-TAILED VOLES

    EPA Science Inventory

    The authors conducted a laboratory toxicity study on house mice and laboratory mice, gray-tailed voles, and deer mice as part of a comprehensive laboratory and field study to field-validate laboratory-based risk assessment of agrichemicals. he single dose oral LD50 for the organo...

  13. 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 ...

  14. Influence of diet on survival of mice.

    PubMed Central

    Fernandes, G; Yunis, E J; Good, R A

    1976-01-01

    The longevity of mice of the (NZB X NZW)F1 (B/W) strain and the DBA/2f strain of mice is dramatically prolonged by dietary restriction. B/W mice are susceptible to, and die at an early age from, immunocomplex nephritis. Mice of the DBA/2f strain are also relatively short-lived. Restriction of caloric intake prolonged life of B/W mice more than did protein restriction. DBA/2f mice showed prolongation of life when the diet was restricted only with respect to protein. Caloric restriction alone prolonged life less in DBA/2f mice than in B/W mice. These observations show that dietary manipulations have profound effects on immunity functions, including inhibition of the development of life-shortening autoimmune disease. PMID:1063408

  15. Stress inoculation modeled in mice

    PubMed Central

    Brockhurst, J; Cheleuitte-Nieves, C; Buckmaster, C L; Schatzberg, A F; Lyons, D M

    2015-01-01

    Stress inoculation entails intermittent exposure to mildly stressful situations that present opportunities to learn, practice and improve coping in the context of exposure psychotherapies and resiliency training. Here we investigate behavioral and hormonal aspects of stress inoculation modeled in mice. Mice randomized to stress inoculation or a control treatment condition were assessed for corticosterone stress hormone responses and behavior during open-field, object-exploration and tail-suspension tests. Stress inoculation training sessions that acutely increased plasma levels of corticosterone diminished subsequent immobility as a measure of behavioral despair on tail-suspension tests. Stress inoculation also decreased subsequent freezing in the open field despite comparable levels of thigmotaxis in mice from both treatment conditions. Stress inoculation subsequently decreased novel-object exploration latencies and reduced corticosterone responses to repeated restraint. These results demonstrate that stress inoculation acutely stimulates glucocorticoid signaling and then enhances subsequent indications of active coping behavior in mice. Unlike mouse models that screen for the absence of vulnerability to stress or presence of traits that occur in resilient individuals, stress inoculation training reflects an experience-dependent learning-like process that resembles interventions designed to build resilience in humans. Mouse models of stress inoculation may provide novel insights for new preventive strategies or therapeutic treatments of human psychiatric disorders that are triggered and exacerbated by stressful life events. PMID:25826112

  16. 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)

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Modeling human epilepsies in mice.

    PubMed

    Noebels, J L

    2001-01-01

    Two categories of mouse models of human epilepsy are now contributing to the experimental analysis of inherited seizure disorders. The first type includes homologous genetic models arrived at in the classic way; the genes from human inherited epilepsy syndromes are cloned, and mice are recreated with functionally identical mutations. The second category involves the reverse strategy: mutating single genes in mice and determining whether the newly created nervous system develops epilepsy. These "gene-forward" models define specific candidate genes that can then be tested for possible involvement in human epilepsies. Spontaneous mutation of genes in mice and other species is also a source for candidate genes. As each of these genes and their physiologic functions is defined, the focus can shift to (a) fully characterizing the clinical epilepsy phenotype, (b) tracing the steps in the molecular pathogenesis of the disorder, and (c) pinpointing molecular targets for early intervention. Along with providing a unique opportunity to understand the mechanisms of inherited epileptogenesis, the mouse models serve as ideal biological test systems to search for novel therapeutic strategies. PMID:11887961

  3. 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

  4. 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

  5. Mice Acquire Flavor Preferences During Shipping

    PubMed Central

    Tordoff, Michael G.; Alarcn, Laura K.; Byerly, Erica A.; Doman, Samantha A.

    2006-01-01

    Vigorous motion can cause rodents to develop flavor aversions and show other signs of malaise. We tested whether a flavor aversion could be induced by shipping mice from an animal breeder to a test site. Boxes of 12 male C57BL/6J mice were shipped ~950 km from Bar Harbor, ME to Philadelphia, PA by truck. For some boxes, the gel provided for hydration was flavored with almond and for others it was flavored with banana. After the journey, the mice were individually housed and allowed to recover for 5 days. They then received a choice between the two flavors of gel. Contrary to expectations, mice preferred the flavor they had previously ingested during shipping. Controls given flavored gel under similar conditions but while stationary did not show a preference. These results suggest that mice find shipping or its sequelae pleasurable. If mice are travel sick this must be inconsequential relative to other components of the shipping experience. PMID:16154605

  6. Models of experimental hypertension in mice.

    PubMed

    Johns, C; Gavras, I; Handy, D E; Salomao, A; Gavras, H

    1996-12-01

    Experimental models of hypertension in various animals are useful in the research of vasoactive mechanisms. Recombinant DNA technology has produced genetically engineered animals, mostly mice, useful in hypertension research. However, the development of hypertensive models in mice is fraught with technical difficulties. We describe here the successful development in mice of two common types of experimental hypertension: the renovascular two-kidney, one clip and mineralocorticoid deoxycorticosterone-salt models. By adapting technology previously used in rats, we succeeded in developing hypertension (defined as systolic pressures higher than 140 mm Hg) in more than 50% of mice so treated. We also adapted the methodology for indirect tail-cuff blood pressure measurements as well as for direct intra-arterial monitoring of blood pressure in conscious, freely moving mice. Application of these techniques in transgenic or gene knockout mice with altered vasoactive hormones or receptors should allow elucidation of the role of the target gene products in various types of hypertension. PMID:8952597

  7. Therapeutic cloning in individual parkinsonian mice.

    PubMed

    Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

    2008-04-01

    Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. 'Therapeutic cloning' is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

  8. Therapeutic cloning in individual parkinsonian mice

    PubMed Central

    Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

    2009-01-01

    Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. Therapeutic cloning is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

  9. Experimental infection in mice with Treponema hyodysenteriae.

    PubMed

    Joens, L A; Glock, R D

    1979-08-01

    Nineteen of 22 female mice (CF1 strain) inoculated intragastrically with Treponema hyodysenteriae developed cecal and colonic lesions consisting of catarrhal inflammation, edema, and occasional hemorrhage. PMID:489130

  10. 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

  11. ACQUIRED IMMUNITY TO CANDIDIASIS IN MICE1

    PubMed Central

    Hasenclever, H. F.; Mitchell, William O.

    1963-01-01

    Hasenclever, H. F. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.) and William O. Mitchell. Acquired immunity to candidiasis in mice. J. Bacteriol. 86:401406. 1963.Some protection to chronic candidiasis in mice was produced by sublethal intraperitoneal infection with Candida albicans and by the injection in incomplete Freund's adjuvant of nonviable Coccidioides immitis spherule fragments. Other pathogenic or nonpathogenic fungi produced little or no protection. Salmonella enteritidis lipopolysaccharide, known to protect mice against the acute toxic manifestations of C. albicans, had no effect upon chronic candidiasis. A factor active in vitro against the growth of C. albicans was shown to be in the serum of resistant mice. PMID:14066415

  12. 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…

  13. 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

  14. Phenotyping Circadian Rhythms in Mice.

    PubMed

    Eckel-Mahan, Kristin; Sassone-Corsi, Paolo

    2015-01-01

    Circadian rhythms take place with a periodicity of 24 hr, 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 hr 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 homecage environment with relative ease. Several tasks commonly used to analyze circadian periodicity and plasticity in mice are presented here including the process of entrainment, determination of tau (period length) in free-running conditions, determination of circadian periodicity in response to light disruption (e.g., jet lag studies), and evaluation of clock plasticity in non-24-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 environmental surroundings. PMID:26331760

  15. 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

  16. 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.

  17. Mice embryology: a microscopic overview.

    PubMed

    Salvadori, Maria Letcia Baptista; Lessa, Thais Borges; Russo, Fabiele Baldino; Fernandes, Renata Avancini; Kfoury, Jos Roberto; Braga, Patricia Cristina Baleeiro Beltro; Miglino, Maria Anglica

    2012-10-01

    In this work, we studied the embryology of mice of 12, 14, and 18 days of gestation by gross observation, light microscopy, and scanning electron microscopy. Grossly, the embryos of 12 days were observed in C-shaped region of the brain, eye pigmentation of the retina, first, second, and third pharyngeal arches gill pit nasal region on the fourth ventricle brain, cervical curvature, heart, liver, limb bud thoracic, spinal cord, tail, umbilical cord, and place of the mesonephric ridge. Microscopically, the liver, cardiovascular system and spinal cord were observed. In the embryo of 14 days, we observed structures that make up the liver and heart. At 18 days of gestation fetuses, it was noted the presence of eyes, mouth, and nose in the cephalic region, chest and pelvic region with the presence of well-developed limbs, umbilical cord, and placenta. Scanning electron microscopy in 18 days of gestation fetuses evidenced head, eyes closed eyelids, nose, vibrissae, forelimb, heart, lung, kidney, liver, small bowel, diaphragm, and part of the spine. The results obtained in this work describe the internal and external morphology of mice, provided by an integration of techniques and review of the morphological knowledge of the embryonic development of this species, as this animal is of great importance to scientific studies. PMID:22730205

  18. 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

  19. 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

  20. 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.

  1. An olfactory discrimination procedure for mice.

    PubMed Central

    Mihalick, S M; Langlois, J C; Krienke, J D; Dube, W V

    2000-01-01

    This paper describes an olfactory discrimination procedure for mice that is inexpensively implemented and leads to rapid discrimination learning. Mice were first trained to dig in small containers of sand to retrieve bits of buried chocolate. For discrimination training, two containers were presented simultaneously for eight trials per session. One container held sand mixed with cinnamon, and the other held sand mixed with nutmeg. Both containers were baited with chocolate buried in the sand. One odor was designated S+, and mice were allowed to dig and retrieve the chocolate from this container. The other odor was S-, and both containers were removed immediately if subjects began to dig in an S- container. After meeting a two-session acquisition criterion, subjects were given a series of discrimination reversals. In Experiment 1, 12 Swiss-Webster mice (6 male and 6 female) acquired the olfactory discrimination in three to five sessions and completed 3 to 10 successive discrimination reversals within a 50-session testing limit. In Experiment 2, subjects were 14 Pah(enu2) mice, the mouse mutant for phenylketonuria; 7 were homozygotes in which the disorder was expressed (PKU), and 7 were heterozygotes with normal metabolism (non-PKU). Thirteen mice completed pretraining in four to seven sessions, acquisition required 3 to 12 sessions, and all mice completed at least three reversals. Learning rates were similar in PKU and non-PKU mice. We discuss issues related to implementation and several potentially useful procedural variations. PMID:10866354

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Retinylamine Benefits Early Diabetic Retinopathy in Mice.

    PubMed

    Liu, Haitao; Tang, Jie; Du, Yunpeng; Lee, Chieh Allen; Golczak, Marcin; Muthusamy, Arivalagan; Antonetti, David A; Veenstra, Alexander A; Amengual, Jaume; von Lintig, Johannes; Palczewski, Krzysztof; Kern, Timothy S

    2015-08-28

    Recent evidence suggests an important role for outer retinal cells in the pathogenesis of diabetic retinopathy (DR). Here we investigated the effect of the visual cycle inhibitor retinylamine (Ret-NH2) on the development of early DR lesions. Wild-type (WT) C57BL/6J mice (male, 2 months old when diabetes was induced) were made diabetic with streptozotocin, and some were given Ret-NH2 once per week. Lecithin-retinol acyltransferase (LRAT)-deficient mice and P23H mutant mice were similarly studied. Mice were euthanized after 2 (WT and Lrat(-/-)) and 8 months (WT) of study to assess vascular histopathology, accumulation of albumin, visual function, and biochemical and physiological abnormalities in the retina. Non-retinal effects of Ret-NH2 were examined in leukocytes treated in vivo. Superoxide generation and expression of inflammatory proteins were significantly increased in retinas of mice diabetic for 2 or 8 months, and the number of degenerate retinal capillaries and accumulation of albumin in neural retina were significantly increased in mice diabetic for 8 months compared with nondiabetic controls. Administration of Ret-NH2 once per week inhibited capillary degeneration and accumulation of albumin in the neural retina, significantly reducing diabetes-induced retinal superoxide and expression of inflammatory proteins. Superoxide generation also was suppressed in Lrat(-/-) diabetic mice. Leukocytes isolated from diabetic mice treated with Ret-NH2 caused significantly less cytotoxicity to retinal endothelial cells ex vivo than did leukocytes from control diabetics. Administration of Ret-NH2 once per week significantly inhibited the pathogenesis of lesions characteristic of early DR in diabetic mice. The visual cycle constitutes a novel target for inhibition of DR. PMID:26139608

  15. Experimental osteoarthritis models in mice.

    PubMed

    Lorenz, Julia; Grssel, Susanne

    2014-01-01

    Osteoarthritis (OA) is a slowly progressing, degenerative disorder of synovial joints culminating in the irreversible destruction of articular cartilage and subchondral bone. It affects almost everyone over the age of 65 and influences life quality of affected individuals with enormous costs to the health care system. Current therapeutic strategies seek to ameliorate pain and increase mobility; however, to date none of them halts disease progression or regenerates damaged cartilage or bone. Thus, there is an ultimate need for the development of new, noninvasive treatments that could substitute joint replacement for late- or end-stage patients. Therefore, osteoarthritis animal models for mimicking of all OA features are important. Mice develop an OA pathology that is comparable to humans, rapidly develop OA due to the short lifetime and show reproducible OA symptoms. They provide a versatile and widely used animal model for analyzing molecular mechanisms of OA pathology. One major advantage over large animal models is the availability of knockout or transgenic mice strains to examine genetic predispositions/contributions to OA.In this chapter, we describe three widely used instability-inducing murine osteoarthritis models. The most common two methods for surgical induction are: (1) destabilization of the medial meniscus (DMM) and (2) anterior cruciate ligament transection (ACLT). In the DMM model, the medial meniscotibial ligament is transected while in the ACLT model the anterior cruciate ligament is destroyed. In the third, chemical induced instability method, intraarticular collagenase is injected into the knee joint. Intraarticular collagenase weakens articular ligaments which cause instability of the joint, and full-blown OA develops within 6 weeks. For morphological evaluation, we correspond mainly to the recommendations of OARSI for histological assessment of osteoarthritis in mouse. For statistical evaluation summed or mean scores of all four knee areas (medial tibial plateau (MTP), medial tibial condyle (MFC), lateral tibial plateau (LTP) or lateral femoral condyle (LFC)), medial and/or lateral regions are used.In future, not only large animal models like guinea pigs, sheep, goats, or horses will be important for a better understanding of osteoarthritis, but especially the mouse model with its rapid development of osteoarthritis and its numerous advantages by providing knockout or transgenic strains will become more and more relevant for drug development and determination of genetic predispositions of osteoarthritis pathology. PMID:25064117

  16. Hydrogen protects mice from radiation induced thymic lymphoma in BALB/c mice.

    PubMed

    Zhao, Luqian; Zhou, Chuanfeng; Zhang, Jian; Gao, Fu; Li, Bailong; Chuai, Yunhai; Liu, Cong; Cai, Jianming

    2011-01-01

    Ionizing radiation (IR) is a well-known carcinogen, however the mechanism of radiation induced thymic lymphoma is not well known. Moreover, an easy and effective method to protect mice from radiation induced thymic lymphoma is still unknown. Hydrogen, or H(2), is seldom regarded as an important agent in medical usage, especially as a therapeutic gas. Here in this study, we found that H(2) protects mice from radiation induced thymic lymphoma in BALB/c mice. PMID:21448340

  17. THERMOREGULATION IN MICE FOLLOWING ACUTE CHLORDIMEFORM ADMINISTRATION

    EPA Science Inventory

    CBA/J mice were injected intraperitoneally with the formamidine insecticide chlordimeform (CDM) while colonic temperature, preferred ambient temperature (Ta), and lethality were monitored. In the first experiment there was a dose-dependent decrease in colonic temperature when mea...

  18. 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

  19. Genetically Engineered Mice by Pronuclear DNA microinjection

    PubMed Central

    DeMayo, Janet L.; Wang, Jie; Liang, Dongcai; Zhang, Ruina; DeMayo, Francesco J.

    2012-01-01

    The generation of transgenic mice by DNA microinjection is a powerful tool to investigate the molecular regulation of gene expression, development, and disease. The power of this technology is that foreign DNA can be introduced into every cell of a developing organism and the phenotypic impact of this genetic modification can be investigated in a system under the constraints of normal development and physiology. The generation of transgenic mice requires the preparation of the transgene DNA construction, collection of one-cell fertilized mouse embryos, injection of the transgene into mouse embryos, and transfer of the surviving embryos. Mice born from such manipulations are then screened for the presence of the transgene. The execution of these procedures requires a highly efficient system otherwise the cost of the generation of these mice can be cost prohibitive. However, the production of these animals can serve as an invaluable research resource. PMID:23024927

  20. The olfactory transcriptomes of mice.

    PubMed

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

    2014-09-01

    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

  1. 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

  2. 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.

  3. Lessons from Tau-Deficient Mice

    PubMed Central

    Ke, Yazi D.; Suchowerska, Alexandra K.; van der Hoven, Julia; De Silva, Dineeka M.; Wu, Christopher W.; van Eersel, Janet; Ittner, Arne; Ittner, Lars M.

    2012-01-01

    Both Alzheimer's disease (AD) and frontotemporal dementia (FTD) are characterized by the deposition of hyperphosphorylated forms of the microtubule-associated protein tau in neurons and/or glia. This unifying pathology led to the umbrella term tauopathies for these conditions, also emphasizing the central role of tau in AD and FTD. Generation of transgenic mouse models expressing human tau in the brain has contributed to the understanding of the pathomechanistic role of tau in disease. To reveal the physiological functions of tau in vivo, several knockout mouse strains with deletion of the tau-encoding MAPT gene have been established over the past decade, using different gene targeting constructs. Surprisingly, when initially introduced tau knockout mice presented with no overt phenotype or malformations. The number of publications using tau knockout mice has recently markedly increased, and both behavioural changes and motor deficits have been identified in aged mice of certain strains. Moreover, tau knockout mice have been instrumental in identifying novel functions of tau, both in cultured neurons and in vivo. Importantly, tau knockout mice have significantly contributed to the understanding of the pathophysiological interplay between A? and tau in AD. Here, we review the literature that involves tau knockout mice to summarize what we have learned so far from depleting tau in vivo. PMID:22720190

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Seasonal acclimation of prairie deer mice.

    PubMed

    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 short-photoperiod 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 degrees 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. PMID:8112876

  14. Lipid transport in cholecystokinin knockout mice.

    PubMed

    King, Alexandra; Yang, Qing; Huesman, Sarah; Rider, Therese; Lo, Chunmin C

    2015-11-01

    Cholecystokinin (CCK) is released in response to lipid feeding and regulates pancreatic digestive enzymes vital to the absorption of nutrients. Our previous reports demonstrated that cholecystokinin knockout (CCK-KO) mice fed for 10 weeks of HFD had reduced body fat mass, but comparable glucose uptake by white adipose tissues and skeletal muscles. We hypothesized that CCK is involved in energy homeostasis and lipid transport from the small intestine to tissues in response to acute treatment with dietary lipids. CCK-KO mice with comparable fat absorption had increased energy expenditure and were resistant to HFD-induced obesity. Using intraduodenal infusion of butter fat and intravenous infusion using Liposyn III, we determined the mechanism of lipid transport from the small intestine to deposition in lymph and adipocytes in CCK-KO mice. CCK-KO mice had delayed secretion of Apo B48-chylomicrons, lipid transport to the lymphatic system, and triglyceride (TG)-derived fatty acid uptake by epididymal fat in response to acute treatment of intraduodenal lipids. In contrast, CCK-KO mice had comparable TG clearance and lipid uptake by white adipocytes in response to TGs in chylomicron-like emulsion. Thus, we concluded that CCK is important for lipid transport and energy expenditure to control body weight in response to dietary lipid feeding. PMID:26171590

  15. Dehydration parameters and standards for laboratory mice.

    PubMed

    Bekkevold, Christine M; Robertson, Kimberly L; Reinhard, Mary K; Battles, August H; Rowland, Neil E

    2013-01-01

    Water deprivation and restriction are common features of many physiologic and behavioral studies; however, there are no data-driven humane standards regarding mice on water deprivation or restriction studies to guide IACUC, investigators, and veterinarians. Here we acutely deprived outbred CD1 mice of water for as long as 48 h or restricted them to a 75% or 50% water ration; physical and physiologic indicators of dehydration were measured. With acute water deprivation, the appearance and attitude of mice deteriorated after 24 h, and weight loss exceeded 15%. Plasma osmolality was increased, and plasma volume decreased with each time interval. Plasma corticosterone concentration increased with duration of deprivation. There were no differences in any dehydration measures between mice housed in conventional static cages or ventilated racks. Chronic water restriction induced no significant changes compared with ad libitum availability. We conclude that acute water deprivation of as long as 24 h produces robust physiologic changes; however, deprivation in excess of 24 h is not recommended in light of apparent animal distress. Although clearly thirsty, mice adapt to chronic water restriction of as much as 50% of the ad libitum daily ration that is imposed over an interval of as long as 8 d. PMID:23849404

  16. Spatial learning by mice in three dimensions

    PubMed Central

    Wilson, Jonathan J.; Harding, Elizabeth; Fortier, Mathilde; James, Benjamin; Donnett, Megan; Kerslake, Alasdair; OLeary, Alice; Zhang, Ningyu; Jeffery, Kate

    2015-01-01

    We tested whether mice can represent locations distributed throughout three-dimensional space, by developing a novel three-dimensional radial arm maze. The three-dimensional radial maze, or radiolarian maze, consists of a central spherical core from which arms project in all directions. Mice learn to retrieve food from the ends of the arms without omitting any arms or re-visiting depleted ones. We show here that mice can learn both a standard working memory task, in which all arms are initially baited, and also a reference memory version in which only a subset are ever baited. Comparison with a two-dimensional analogue of the radiolarian maze, the hexagon maze, revealed equally good working-memory performance in both mazes if all the arms were initially baited, but reduced working and reference memory in the partially baited radiolarian maze. This suggests intact three-dimensional spatial representation in mice over short timescales but impairment of the formation and/or use of long-term spatial memory of the maze. We discuss potential mechanisms for how mice solve the three-dimensional task, and reasons for the impairment relative to its two-dimensional counterpart, concluding with some speculations about how mammals may represent three-dimensional space. PMID:25930216

  17. Pulmonary alveolar proteinosis in SCID mice.

    PubMed

    Jennings, V M; Dillehay, D L; Webb, S K; Brown, L A

    1995-09-01

    Pulmonary alveolar proteinosis (PAP) is an uncommon disorder of unknown origin in which the alveoli are filled with lipoproteinaceous material, including surfactant. We have characterized a spontaneously occurring lesion in the lungs of CB.17 scid/scid mice which resembles PAP in humans. Lungs from 45 severe combined immunodeficient (SCID) mice were evaluated by light and electron microscopy and immunohistochemistry. Lung lavage fluid was evaluated biochemically and for the presence of surfactant protein A (SP-A) and B (SP-B) by enzyme-linked immunosorbent assay and Western blot. Light microscopy showed varying amounts of a homogeneous to granular proteinaceous material in alveolar spaces. This material was eosinophilic by hematoxylin and eosin stain and was periodic acid-Schiff (PAS) positive. Ultrastructurally, the material was predominantly homogeneous with areas of a lamellated pattern that resembled surfactant. Biochemical analysis revealed 2.7- and 3.6-fold increases in the surfactant-associated phospholipids phosphatidylcholine and disaturated phosphatidylcholine respectively, when affected SCID mice were compared with control mice. Immunohistochemical staining of lung tissue and Western blot and enzyme-linked immunosorbent assay of lavage fluid showed marked increases in SP-A and SP-B in comparison with controls. These results suggest that SCID mice have a defect in surfactant homeostasis that resembles PAP in humans and may serve as an animal model in further elucidating the pathogenesis of this disease. PMID:7654386

  18. Experimental Adaptation of Salmonella typhimurium to Mice

    PubMed Central

    Nilsson, Annika I.; Kugelberg, Elisabeth; Berg, Otto G.; Andersson, Dan I.

    2004-01-01

    Experimental evolution is a powerful approach to study the dynamics and mechanisms of bacterial niche specialization. By serial passage in mice, we evolved 18 independent lineages of Salmonella typhimurium LT2 and examined the rate and extent of adaptation to a mainly reticuloendothelial host environment. Bacterial mutation rates and population sizes were varied by using wild-type and DNA repair-defective mutator (mutS) strains with normal and high mutation rates, respectively, and by varying the number of bacteria intraperitoneally injected into mice. After <200 generations of adaptation all lineages showed an increased fitness as measured by a faster growth rate in mice (selection coefficients 0.110.58). Using a generally applicable mathematical model we calculated the adaptive mutation rate for the wild-type bacterium to be >10?6/cell/generation, suggesting that the majority of adaptive mutations are not simple point mutations. For the mutator lineages, adaptation to mice was associated with a loss of fitness in secondary environments as seen by a reduced metabolic capability. During adaptation there was no indication that a high mutation rate was counterselected. These data show that S. typhimurium can rapidly and extensively increase its fitness in mice but this niche specialization is, at least in mutators, associated with a cost. PMID:15579674

  19. 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 (25C) 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.

  20. Visualizing influenza virus infection in living mice.

    PubMed

    Pan, Weiqi; Dong, Zhenyuan; Li, Feng; Meng, Weixu; Feng, Liqiang; Niu, Xuefeng; Li, Chufang; Luo, Qinfang; Li, Zhengfeng; Sun, Caijun; Chen, Ling

    2013-01-01

    Preventing and treating influenza virus infection remain a challenge because of incomplete understanding of the host-pathogen interactions, limited therapeutics and lack of a universal vaccine. So far, methods for monitoring the course of infection with influenza virus in real time in living animals are lacking. Here we report the visualization of influenza viral infection in living mice using an engineered replication-competent influenza A virus carrying luciferase reporter gene. After intranasal inoculation, bioluminescence can be detected in the chest and nasopharyngeal passage of living mice. The intensity of bioluminescence in the chest correlates with the dosage of infection and the viral load in the lung. Bioluminescence in the chest of infected mice diminishes on antiviral treatment. This work provides a novel approach that enables real-time study of influenza virus infection and effects of antiviral therapeutics in living animals. PMID:24022374

  1. 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.

  2. 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.

  3. Visualizing influenza virus infection in living mice

    PubMed Central

    Pan, Weiqi; Dong, Zhenyuan; Li, Feng; Meng, Weixu; Feng, Liqiang; Niu, Xuefeng; Li, Chufang; Luo, Qinfang; Li, Zhengfeng; Sun, Caijun; Chen, Ling

    2013-01-01

    Preventing and treating influenza virus infection remain a challenge because of incomplete understanding of the hostpathogen interactions, limited therapeutics and lack of a universal vaccine. So far, methods for monitoring the course of infection with influenza virus in real time in living animals are lacking. Here we report the visualization of influenza viral infection in living mice using an engineered replication-competent influenza A virus carrying luciferase reporter gene. After intranasal inoculation, bioluminescence can be detected in the chest and nasopharyngeal passage of living mice. The intensity of bioluminescence in the chest correlates with the dosage of infection and the viral load in the lung. Bioluminescence in the chest of infected mice diminishes on antiviral treatment. This work provides a novel approach that enables real-time study of influenza virus infection and effects of antiviral therapeutics in living animals. PMID:24022374

  4. 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.

  5. 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.

  6. Mutagenicity of secalonic acid D in mice.

    PubMed

    Reddy, C S; Reddy, R V; Chan, P K; Hayes, A W

    1980-11-01

    Secalonic acid D is an acutely toxic and teratogenic mycotoxin, produced by Penicillium oxalicum in corn. Two rodent mutagenicity tests, the dominant lethal test designed to evaluate male germ cell mutations and the micronucleus test designed to evaluate somatic cell mutations, were conducted in mice to assess the carcinogenic potential of secalonic acid D. Data obtained indicate that the positive control compound triethylene melamine (TEM) induced dominant lethal mutations during weeks 1 through 4 after administration to male mice and also resulted in a greatly increased population of micronucleated polychromatic (immature) erythrocytes in bone marrow of treated male mice. Secalonic acid D, however, failed to induce dominant lethal mutations but produced a slight but statistically significant increase in the number of micronucleated polychromatic erythrocytes in mouse bone marrow at maximally tolerated doses. It is concluded that secalonic acid D may e weakly mutagenic in a mouse somatic cell mutation system. PMID:7217855

  7. 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.

  8. The somatotropic axis and longevity in mice.

    PubMed

    Brown-Borg, H M

    2015-09-15

    The somatotropic signaling pathway has been implicated in aging and longevity studies in mice and other species. The physiology and lifespans of a variety of mutant mice, both spontaneous and genetically engineered, have contributed to our current understanding of the role of growth hormone and insulin-like growth factor I on aging-related processes. Several other mice discovered to live longer than their wild-type control counterparts also exhibit differences in growth factor levels; however, the complex nature of the phenotypic changes in these animals may also impact lifespan. The somatotropic axis impacts several pathways that dictate insulin sensitivity, nutrient sensing, mitochondrial function, and stress resistance as well as others that are thought to be involved in lifespan regulation. PMID:26219867

  9. High resolution colonoscopy in live mice.

    PubMed

    Becker, C; Fantini, M C; Neurath, M F

    2006-01-01

    Endoscopy in humans is a powerful method for physicians to examine the gut for inflammatory or neoplastic changes. In medical and immunological research, animal models of intestinal diseases are established key tools to investigate the mucosal immune system, colitis and cancer development in the gut. Moreover, such models represent valid systems for testing of novel drugs. In the past, mice had to be killed in order to analyze colitis activity and tumor development. The following protocol describes a method to perform high resolution endoscopic monitoring of live mice. Mice developing colitis or colonic tumors are anesthetized and examined with a miniendoscope. The endoscope is introduced via the anus and the colon is carefully insufflated with an air pump. Endoscopic pictures obtained are of high quality and allow the monitoring and grading of tumors and inflammation. In addition, colonic biopsies can be taken. This protocol can be completed within 1 h. PMID:17406549

  10. Engineering humanized mice for improved hematopoietic reconstitution

    PubMed Central

    Drake, Adam C; Chen, Qingfeng; Chen, Jianzhu

    2012-01-01

    Humanized mice are immunodeficient animals engrafted with human hematopoietic stem cells that give rise to various lineages of human blood cells throughout the life of the mouse. This article reviews recent advances in the generation of humanized mice, focusing on practical considerations. We discuss features of different immunodeficient recipient mouse strains, sources of human hematopoietic stem cells, advances in expansion and genetic modification of hematopoietic stem cells, and techniques to modulate the cytokine environment of recipient mice, in order to enhance reconstitution of specific human blood lineage cells. We highlight the opportunities created by new technologies and discuss practical considerations on how to make best use of the widening array of basic models for specific research applications. PMID:22425741

  11. 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

  12. Transgenic sickle mice have vascular inflammation.

    PubMed

    Belcher, John D; Bryant, Christopher J; Nguyen, Julia; Bowlin, Paul R; Kielbik, Miroslaw C; Bischof, John C; Hebbel, Robert P; Vercellotti, Gregory M

    2003-05-15

    Inflammation may play an essential role in vaso-occlusion in sickle cell disease. Sickle patients have high white counts and elevated levels of serum C-reactive protein (CRP), cytokines, and adhesion molecules. In addition, circulating endothelial cells, leukocytes, and platelets are activated. We examined 4 transgenic mouse models expressing human alpha- and sickle beta-globin genes to determine if they mimic the inflammatory response seen in patients. These mouse models are designated NY-S, Berk-S(Antilles), NY-S/S(Antilles) (NY-S x Berk-S(Antilles)), and Berk-S. The mean white counts were elevated 1.4- to 2.1-fold (P mice, but not in the NY-S mice compared with controls. Serum amyloid P-component (SAP), an acute-phase response protein with 60% to 70% sequence homology to CRP, was elevated 8.5- to 12.1-fold (P mice. Similarly, serum interleukin-6 (IL-6) was elevated 1.6- to 1.9-fold (P mice. Ribonuclease protection assays (RPAs) demonstrated VCAM mRNA also was elevated in sickle mice 1.2- to 1.4-fold (P mice are good models to study vascular inflammation and the potential benefit of anti-inflammatory therapies to prevent vaso-occlusion in sickle cell disease. PMID:12543857

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Pharmacokinetics of memantine in rats and mice

    PubMed Central

    Beconi, Maria G.; Howland, David; Park, Larry; Lyons, Kathryn; Giuliano, Joseph; Dominguez, Celia; Munoz-Sanjuan, Ignacio; Pacifici, Robert

    2012-01-01

    To evaluate the potential of memantine as a therapeutic agent for Huntingtons disease (HD) we have undertaken a series of in vitro, ex vivo and whole animal studies to characterize its pharmacokinetics (PK) and pharmacodynamics (PD) in rats and mice. Results from these studies will enable determination of memantine exposures needed to engage the related functional PD marker and help predict the dose regimen for clinical trials to test its proposed mechanism of action; the selective blockade of extrasynaptic, but not synaptic, NMDA receptors. The studies reported here describe the PK of memantine in rats and mice at low (1 mg/kg) and high (10 mg/kg) doses. Our studies indicate that the clearance mechanisms of memantine in rats and mice are different from those in human, and that clearance needs to be taken into account when extrapolating to the human. In rats only, there is a significant metabolic contribution to memantine clearance at lower dose levels. While memantine is primarily cleared renally in all three species, the proportion of total systemic clearance above the glomerular filtration rate (GFR) is much higher in rats and mice (~13, 4.5, and 1.4 times higher than GFR in rats, mice, and humans, respectively), suggesting that the contribution of active transport to memantine elimination in rats and mice is more significant than in the human. In rats and mice, memantine had a short half-life (<4 h) and steep Cmax/Cmin ratios (>100). In the human, the half-life of memantine was reported to be very long (60-80 h) with a Cmax/Cmin ratio at steady state concentrations of ~1.5. A small change in the clearance of memantine - for example due to renal impairment or competition for the elimination pathway with a co-administered drug - will likely affect exposure and, therefore, the selectivity of memantine on NMDA receptors . The PK differences observed between these species demonstrate that the PK in mice and rats cannot be directly extrapolated to the human. Further, the relationship between the plasma concentration (and therefore dose) needed to elicit a mechanism-related in vivo functional effect (PD readout) while maintaining the selectivity of the extrasynaptic blockade of the NMDA receptors needs to be established before clinical trials can be appropriately planned. PMID:22307216

  18. 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; Hkfelt, 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

  19. Acute stress affects the physiology and behavior of allergic mice.

    PubMed

    Sutherland, M A; Shome, G P; Hulbert, L E; Krebs, N; Wachtel, M; McGlone, J J

    2009-09-01

    Physical and psychological stressors have been implicated in acute asthma exacerbation. The objective of the current study was to determine the effects of forced swimming stress (FST) on allergic pulmonary inflammation in BALB/c mice. Eighty female mice were allocated to one of four treatments arranged in a 2 x 2 factorial consisting of two levels of allergy and two levels of stress. The effects of stress and allergy were assessed by examination of cytokines and leukocyte differentials in the bronchoalveolar lavage fluid, corticosterone and immunoglobulin (Ig) E in the plasma, leukocyte differentials in the peripheral blood, natural killer cytotoxicity, and histopathology of the lungs. Behavior was recorded during the FST. Stress and allergy increased plasma corticosterone in mice. Allergy increased IgE concentrations and pulmonary inflammation. Interleukin-4 was greater among allergic stressed and non-stressed mice and stressed, non-allergic mice compared with non-stressed, non-allergic mice. Interleukin-5 (IL-5) and 6 (IL-6) were greater among allergic stressed and non-stressed mice compared with non-allergic mice. Interleukin-5 and 6 were reduced among stressed-allergic mice compared with non-stressed, allergic mice. Stress and allergy shifted mice towards a T-helper 2 response as shown by increased interleukin-4. Stress reduced IL-5 and IL-6 in allergic mice but not non-allergic mice. Pulmonary inflammation was not reduced among allergic stressed mice in spite of elevated glucocorticoids. Mice induced to be allergic responded to FST differently than non-allergic mice. Our findings suggest that stress induces a differential response among allergic and non-allergic mice. PMID:19527741

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. The tumor spectrum in FHIT-deficient mice.

    PubMed

    Zanesi, N; Fidanza, V; Fong, L Y; Mancini, R; Druck, T; Valtieri, M; Rdiger, T; McCue, P A; Croce, C M; Huebner, K

    2001-08-28

    Mice carrying one inactivated Fhit allele (Fhit +/- mice) are highly susceptible to tumor induction by N-nitrosomethylbenzylamine, with 100% of Fhit +/- mice exhibiting tumors of the forestomach/squamocolumnar junction vs. 25% of Fhit +/+ controls. In the current study a single N-nitrosomethylbenzylamine dose was administered to Fhit +/+, +/-, and -/- mice to compare carcinogen susceptibility in +/- and -/- Fhit-deficient mice. At 29 weeks after treatment, 7.7% of wild-type mice had tumors. Of the Fhit -/- mice 89.5% exhibited tumors (average 3.3 tumors/mouse) of the forestomach and squamocolumnar junction; half of the -/- mice had medium (2 mm diameter) to large (>2 mm) tumors. Of the Fhit +/- mice 78% exhibited tumors (average 2.4 tumors/mouse) and 22% showed medium to large tumors. Untreated Fhit-deficient mice have been observed for up to 2 years for spontaneous tumors. Fhit +/- mice (average age 21 mo) exhibit an average of 0.94 tumors of different types; Fhit -/- mice (average age 16 mo) also showed an array of tumors (average 0.76 tumor/mouse). The similar spontaneous and induced tumor spectra observed in mice with one or both Fhit alleles inactivated suggests that Fhit may be a one-hit tumor suppressor gene in some tissues. PMID:11517343

  5. Mycobacterium lepraemurium infection of nude athymic (nu/nu) mice.

    PubMed Central

    Lefford, M J

    1985-01-01

    Nude athymic (nu/nu) mice on a BALB/c background and their heterozygous euthymic litter mates (nu/+) were infected with either 10(8) or 10(6) Mycobacterium lepraemurium organisms intravenously or in the left hind footpad (LHF). After LHF infection with 10(8) M. lepraemurium organisms, nu/+ mice slowly developed a response that consisted of LHF swelling and local resistance to Listeria monocytogenes. The lower inoculum induced a proportionately lower response in nu/+ mice, but the nu/nu mice developed neither LHF swelling nor resistance to L. monocytogenes in response to either dose of M. lepraemurium. Counts of M. lepraemurium in the LHF revealed no difference between the nu/+ mice and nu/nu mice. After intravenous infection the nu/+ mice developed splenomegaly, but did not otherwise differ from nu/nu mice with respect to resistance to intravenous challenge with L. monocytogenes or growth of M. lepraemurium in the spleen. In light of the poor responsiveness of nu/+ mice in this experiment, they were then compared with CB6 and B6D2 mice, which are genetically susceptible and resistant to M. lepraemurium, respectively. These mice were infected with either 10(8) or 10(6) M. lepraemurium cells or 10(6) Mycobacterium bovis BCG cells in the LHF. Once again the nu/+ mice responded poorly to M. lepraemurium, the CB6 mice responded very strongly, and the B6D2 mice gave an intermediate response with respect to LHF swelling and resistance to L. monocytogenes. However, M. lepraemurium grew to higher numbers in the LHF of nu/+ and CB6 mice than in B6D2 mice, revealing, in CB6 mice, a dissociation between resistance to L. monocytogenes and M. lepraemurium. All three mouse strains responded strongly to M. bovis BCG, but there was a suggestion that nu/+ mice might be more susceptible to this agent than the other two strains. I concluded that the failure of nu/+ mice to restrict the growth of M. lepraemurium more than nu/nu mice was due to the intrinsic genetic susceptibility of both types of mice. In effect, the nu/+ mice behaved like nu/nu mice, as if they too were deficient in T lymphocytes that were responsive to M. lepraemurium. PMID:3891623

  6. Behavior of captive white-footed mice.

    PubMed

    Kavanau, J L

    1967-03-31

    Detailed studies of the behavior of captive white-footed mice have cast a number of old problems in new perspectives. Many responses of small captive mammals cannot be interpreted at face value because of severe distortions of behavior that are caused by depriving the wild animal of natural outlets for activity. Confined animals are likely to seize upon and repeatedly exercise virtually any opportunities to modify (and alter their relationships with) their surroundings. In addition they have a strong tendency to counteract nonvolitional and "unexpected" deviations from the status quo. As a result, their responses do not bear an immutable relationship to the nature of the stimulus or other variable being modified; stimuli and activities that are rewarding in certain circumstances are avoided in others. These aspects of behavior have been illustrated by studies of nest occupancy, running in motordriven wheels, and control of intensity of illumination. The results of the control-of-illumination studies suggest the complex interplay of tendencies to modify features of the environment, to avoid conditions imposed compulsorily, and to select preferred levels of illumination. The importance of split-second timing, coordination, and quick reflex actions in the running of activity wheels is indicated by the fact that experienced white-footed mice prefer running in square "wheels" and wheels with hurdles to running in plain round wheels. The relatively conservative behavior of these mice in selecting between multiple sources of food and water and different types of activity wheels suggests the need for careful experimental design in free-choice studies with inexperienced animals. The tendency of trained animals to give some so-called "incorrect" responses even after long experience can be interpreted most reasonably in terms of the adaptive value of a certain degree of variability of behavior in the wild. White-footed mice readily master complex regimes in which several different levers and shutters must be pressed or rotated in certain sequences within seconds for different rewards. They quickly learn to traverse mazes containing hundreds of blind alleys and do so frequently without extrinsic reward. It is unlikely that these remarkable learning performances even begin to approach the capacities of the animals. When two female mice having markedly different solitary behavior patterns were placed in consort, the behavior of each changed, becoming more like that of the other, and the animals showed a strong tendency to remain in each other's company. The behavior of mice in enclosures of great extent casts doubt upon the postulate that hunger and thirst play leading roles in the motivation of wide-ranging locomotor movements. Accordingly, studies of deprived domestic animals in simple mazes may have but limited significance for understanding the behavior of wild and relatively unconfined animals. The existence of marked individual differences between mice selected at random from wild populations sounds the need for a cautious approach in the interpretation of results obtained with highly inbred domestic animals. The relatively uniform behavior of inbred strains represents only a small fragment of the total response spectrum for the species and probably has minimal significance for adaptation and evolution in the wild. When allowed to control the intensity of illumination by operating a series of switches, white-footed mice establish a roughly 24-hour regime consistent with that experienced in the wild, namely dim light during periods of activity and very dim light during periods of inactivity. Consistent with this finding, when exposed to a dim-dark light cycle, the mice are active during the dim phase, not in darkness. Artificial twilight transitions of both constant and varying color temperature have several marked effects upon the activity of white-footed mice. The existence of a strong orienting influence of dim light on the direction of wheel-running suggests that mice in the wild use the twilight

  7. SULFOLANE-INDUCED HYPOTHERMIA ENHANCES SURVIVABILITY IN MICE

    EPA Science Inventory

    Mice injected intraperitoneally with sulfolane (tetrahydrothiophene-1, 1-dioxide) undergo a decrease in metabolic rate and body temperature. If given the opportunity, mice treated with sulfolane preferentially seek a cool ambient temperature. At a warm ambient temperature (35 C) ...

  8. 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

  9. 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

  10. 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

  11. Visual behavior: mice run from overhead danger.

    PubMed

    Mnch, Thomas A

    2013-10-21

    Mice show an innate protective behavior to looming shadows approaching from above: they either run for cover or freeze in place. This newly discovered 'looming response' adds to the repertoire of stereotyped behaviors that can be utilized to study visual pathways. PMID:24156812

  12. 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...

  13. Pathogenicity of Allescheria boydii for Mice

    PubMed Central

    Lupan, David M.; Cazin, John

    1973-01-01

    Allescheria boydii and its imperfect state, Monosporium apiospermum, were studied to determine whether asexual or sexual strains might exhibit different pathogenic potentials for mice. Six different strains of the fungus were inoculated into mice by the intravenous, intracerebral, intraperitoneal, and intranasal routes. Cortisone-treated mice regularly developed infections after inoculation by any of the routes tested. Mice that had not been treated with cortisone were most susceptible to infection by the intravenous route and least susceptible to infection by the intranasal or intraperitoneal route; nevertheless, all animals that did not receive cortisone were considerably more resistant to infection by the fungus than were comparable groups of cortisone-treated animals. Pathogenicity of the fungus appears to be strain dependent and entirely unrelated to its sexual or asexual form. Studies made to determine accurate viable spore counts of the fungus revealed that the highest viable spore count was generally observed using Sabouraud dextrose agar or potato dextrose agar at an incubation temperature of 37 C for a period of 5 days. Images PMID:4795949

  14. Clinically relevant frailty index for mice.

    PubMed

    Liu, Haiming; Graber, Ted G; Ferguson-Stegall, Lisa; Thompson, LaDora V

    2014-12-01

    Frailty is a clinical syndrome associated with the aging process and adverse outcomes. The purpose of this short report was to initiate the development of a Frailty Index in 27- to 28-month-old C57BL/6 mice that matched the clinical criteria used in humans (weakness, slow walking speed, low activity level, poor endurance). The selected criteria included grip strength, walking speed, physical activity, and endurance. The criteria in mice were evaluated by the inverted-cling grip test, rotarod test, voluntary wheel running, and derived endurance scores. Each criterion had a designated cutoff point (1.5 SD below the cohort mean) to identify the mice with the lowest performance. If a mouse presented with three of the criteria scores below the cutoff points, it was identified as frail. Mild frailty was designated if two criteria were below the cutoff points. In this mouse cohort, one mouse was identified as frail and one was mildly frail. This prevalence of 9% frailty is consistent with the prevalence of frailty in humans at the same survival age. Collectively, our selected criterion, cutoff point, and Frailty Index provide a potential standardized definition for frailty in mice that is consistent with the operational definition of frailty in humans. PMID:24336799

  15. Color vision: mice see hue too.

    PubMed

    Conway, Bevil R

    2007-06-19

    A transgenic mouse has been generated with three cone types, instead of the normal murine two. Remarkably, some of these mice use the extra cone to make trichromatic color discriminations similar to those that are the basis of human color vision. PMID:17580074

  16. Abnormal trigeminal sensory processing in obese mice.

    PubMed

    Rossi, Heather L; Broadhurst, Kimberly A; Luu, Anthony S K; Lara, Orlando; Kothari, Sunny D; Mohapatra, Durga P; Recober, Ana

    2016-01-01

    Obesity is associated with several pain disorders including headache. The effects of obesity on the trigeminal nociceptive system, which mediates headache, remain unknown. We used 2 complementary mouse models of obesity (high-fat diet and leptin deficiency) to examine this. We assessed capsaicin-induced nocifensive behavior and photophobia in obese and control mice. Calcium imaging was used to determine the effects of obesity on the activity of primary trigeminal afferents in vitro. We found that obese mice had a normal acute response to a facial injection of capsaicin, but they developed photophobic behavior at doses that had no effect on control mice. We observed higher calcium influx in cultured trigeminal ganglia neurons from obese mice and a higher percentage of medium to large diameter capsaicin-responsive cells. These findings demonstrate that obesity results in functional changes in the trigeminal system that may contribute to abnormal sensory processing. Our findings provide the foundation for in-depth studies to improve the understanding of the effects of obesity on the trigeminal system and may have implications for the pathophysiology of headache disorders. PMID:26397933

  17. 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

  18. 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

  19. 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.…

  20. 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.

  1. 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).

  2. 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.

  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. Neural Tube Defects In Mice Exposed To Tap Water

    PubMed Central

    Mallela, Murali K; Werre, Stephen R; Hrubec, Terry C

    2010-01-01

    In May of 2006 we suddenly began to observe neural tube defects (NTDs) in embryos of untreated control mice. We hypothesized the mice were being exposed unknowingly to a teratogenic agent and investigated the cause. Our results suggested that NTDs were not resulting from bedding material, feed, strain or source of the mice. Additionally, mice were negative for routine and comprehensive screens of pathogens. To further test whether the NTDs resulted from infectious or genetic cause localized to our facility, we obtained three strains of timed pregnant mice from commercial suppliers located in 4 different states. All strains and sources of mice arrived in our laboratory with NTDs, implying that commercially available mice were possibly exposed to a teratogen prior to purchase. Our investigation eventually concluded that exposure to tap water was causing the NTDs. The incidence of NTDs was greatest in purchased mice provided tap water and lowest in purchased mice provided distilled deionized water (DDI). Providing mice DDI water for two generations (F2-DDI) eliminated the NTDs. When F2-DDI mice were provided tap water from three different urban areas prior to breeding, their offspring again developed NTDs. Increased length of exposure to tap water significantly increased the incidence of NTDs. These results indicate that a contaminant in municipal tap water is likely causing NTDs in mice. The unknown teratogen appears to have a wide geographic distribution but has not yet been identified. Water analysis is currently underway to identify candidate contaminants that might be responsible for the malformations. PMID:20549630

  5. Neural tube defects in mice exposed to tap water.

    PubMed

    Mallela, Murali K; Werre, Stephen R; Hrubec, Terry C

    2011-11-01

    In May of 2006 we suddenly began to observe neural tube defects (NTDs) in embryos of untreated control mice. We hypothesized the mice were being exposed unknowingly to a teratogenic agent and investigated the cause. Our results suggested that NTDs were not resulting from bedding material, feed, strain, or source of the mice. Additionally, mice were negative for routine and comprehensive screens of pathogens. To further test whether the NTDs resulted from infectious or genetic cause localized to our facility, we obtained three strains of timed pregnant mice from commercial suppliers located in four different states. All strains and sources of mice arrived in our laboratory with NTDs, implying that commercially available mice were possibly exposed to a teratogen prior to purchase. Our investigation eventually concluded that exposure to tap water was causing the NTDs. The incidence of NTDs was greatest in purchased mice provided tap water and lowest in purchased mice provided distilled deionized water (DDI). Providing mice DDI water for two generations (F2-DDI) eliminated the NTDs. When F2-DDI mice were provided tap water from three different urban areas prior to breeding, their offspring again developed NTDs. Increased length of exposure to tap water significantly increased the incidence of NTDs. These results indicate that a contaminant in municipal tap water is likely causing NTDs in mice. The unknown teratogen appears to have a wide geographic distribution but has not yet been identified. Water analysis is currently underway to identify candidate contaminants that might be responsible for the malformations. PMID:20549630

  6. Rhodopsin Signaling and Organization in Heterozygote Rhodopsin Knockout Mice*S

    PubMed Central

    Liang, Yan; Fotiadis, Dimitrios; Maeda, Tadao; Maeda, Akiko; Modzelewska, Anna; Filipek, Slawomir; Saperstein, David A.; Engel, Andreas; Palczewski, Krzysztof

    2005-01-01

    Rhodopsin (Rho) resides within internal membrane structures called disc membranes that are found in the rod outer segments (ROS) of photoreceptors in the retina. Rho expression is essential for formation of ROS, which are absent in knockout Rho?/ ? mice. ROS of mice heterozygous for the Rho gene deletion (Rho+/?) may have a lower Rho density than wild type (WT) membranes, or the ROS structure may be reduced in size due to lower Rho expression. Here, we present evidence that the smaller volume of ROS from heterozygous mice is most likely responsible for observed electrophysiological response differences. In Rho+/? mice as compared with age-matched WT mice, the length of ROS was shorter by 3040%, and the average diameter of ROS was reduced by ~20%, as demonstrated by transmission and scanning electron microscopy. Together, the reduction of the volume of ROS was ~60% in Rho+/? mice. Rho content in the eyes was reduced by ~43% and 11-cis-retinal content in the eye was reduced by ~38%, as determined by UV-visible spectroscopy and retinoid analysis, respectively. Transmission electron microscopy of negatively stained disc membranes from Rho+/? mice indicated a typical morphology apart from the reduced size of disc diameter. Power spectra calculated from disc membrane regions on such electron micrographs displayed a diffuse ring at ~4.5 nm?1, indicating paracrystallinity of Rho. Atomic force microscopy of WT and Rho+/? disc membranes revealed, in both cases, Rho organized in paracrystalline and raftlike structures. From these data, we conclude that the differences in physiological responses measured in WT and Rho+/? mice are due to structural changes of the whole ROS and not due to a lower density of Rho. PMID:15337746

  7. 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

  8. 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

  9. 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

  10. Motor Unit Abnormalities in Dystonia musculorum Mice

    PubMed Central

    Ryan, Scott D.; Sato, Tadasu; Kothary, Rashmi

    2011-01-01

    Dystonia musculorum (dt) is a mouse inherited sensory neuropathy caused by mutations in the dystonin gene. While the primary pathology lies in the sensory neurons of dt mice, the overt movement disorder suggests motor neurons may also be affected. Here, we report on the contribution of motor neurons to the pathology in dt27J mice. Phenotypic dt27J mice display reduced alpha motor neuron cell number and eccentric alpha motor nuclei in the ventral horn of the lumbar L1 spinal cord region. A dramatic reduction in the total number of motor axons in the ventral root of postnatal day 15 dt27J mice was also evident. Moreover, analysis of the trigeminal nerve of the brainstem showed a 2.4 fold increase in number of degenerating neurons coupled with a decrease in motor neuron number relative to wild type. Aberrant phosphorylation of neurofilaments in the perikaryon region and axonal swellings within the pre-synaptic terminal region of motor neurons were observed. Furthermore, neuromuscular junction staining of dt27J mouse extensor digitorum longus and tibialis anterior muscle fibers showed immature endplates and a significant decrease in axon branching compared to wild type littermates. Muscle atrophy was also observed in dt27J muscle. Ultrastructure analysis revealed amyelinated motor axons in the ventral root of the spinal nerve, suggesting a possible defect in Schwann cells. Finally, behavioral analysis identified defective motor function in dt27J mice. This study reveals neuromuscular defects that likely contribute to the dt27J pathology and identifies a critical role for dystonin outside of sensory neurons. PMID:21698255

  11. p53 influences mice skeletal development.

    PubMed

    Ohyama, K; Chung, C H; Chen, E; Gibson, C W; Misof, K; Fratzl, P; Shapiro, I M

    1997-01-01

    The p53 tumor suppressor gene encodes a transcriptional activator whose targets include genes that regulate cell cycle progression and apoptosis. Since we have shown that a critical event in the life history of the chondrocyte is programmed cell death, we asked the question: does loss of the p53 gene influence skeletogenesis? Female p53(+/-) mice were mated with p53(+/-) male mice and 17-day-old fetal mice were studied. Exencephaly was the most profound skeletal defect of the p53 null mutation. This defect was due to failure of formation of the bones that comprise the mouse calvarium. There was also loss of the hyoid bone, and defective mineralization of the manubrium sternum and the terminal phalanges. In the homozygous state (-/-), in the absence of exencephaly, the number of skeletal deformities was markedly reduced. Aside from the gross changes associated with null status, the mutants exhibited alterations in bone length and width. Small differences in the size and orientation of the mineral crystals in embryonic bone, as evaluated by small-angle X-ray scattering, were found to disappear after birth. To explain these observations, we evaluated the extent of apoptosis in the tibial growth plates using the TUNEL stain. In the growth plate of the p53(-/-) homozygote, there was minimal labeling of the hypertrophic layer. Since the p53(-/-) TUNEL stain pattern at 17 days was very similar to the pattern of labeling of the p53(+/+) at 15 days, we concluded that the growth defect reflected a delay in cartilage maturation rather than a change in chondrocyte phenotype. On this basis, we predict that after birth, in mice that survive, differences in bone length would become minimal, and at maturity, the length of the long bones of (+/+) and (-/-) mice would be similar. PMID:9493073

  12. 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

  13. Age and aerobic performance in deer mice.

    PubMed

    Chappell, Mark A; Rezende, Enrico L; Hammond, Kimberly A

    2003-04-01

    Age impacts the phenotype of all multicellular animals, but lifetime changes in physiological traits are poorly understood for all but a few species. Here, we describe a cross-sectional study of age effects on body composition, aerobic performance and ventilation in deer mice Peromyscus maniculatus. This species lives considerably longer in captivity (in excess of 5 years) than most laboratory rodents, and the adaptational biology of its aerobic physiology is well studied. Our deer mice grew throughout life, and, as is typical for mammals, their basal metabolic rate (BMR) and maximal oxygen consumption in exercise ((VO(2)max)) and thermogenesis ((VO(2)sum)) increased as power functions of mass. Age did not affect BMR, but we found abrupt decreases in growth rate, (VO(2)max) and (VO(2)sum) at approximately 485 days of age, and the mass-adjusted maximal aerobic performance of old mice (5 years of age) was 20% ((VO(2)max)) to 35% ((VO(2)sum)) less than that of young animals. Breathing frequency (f) and oxygen extraction (E(O(2))) also declined with age but did not change abruptly. However, there were no consistent age-related changes in tidal volume (V(T)) or minute volume ((Vmin)) after accounting for the effects of mass and (VO(2)sum). Age influenced several aspects of body composition (lean and fat mass). However, these changes were insufficient to explain the age-related declines in aerobic performance, suggesting that mass-specific oxidative capacity of lean tissue decreased with age. The performance changes we found could engender substantial reductions in the mobility and thermal tolerances of old deer mice. However, very few wild mice are likely to survive to ages where substantial performance decreases occur, so these declines are probably not subjected to strong selection in natural populations. PMID:12604582

  14. Defective bone microstructure in hydronephrotic mice: a histomorphometric study in ICR/Mlac-hydro mice.

    PubMed

    Suntornsaratoon, Panan; Wongdee, Kannikar; Tiyasatkulkovit, Wacharaporn; Ampawong, Sumate; Krishnamra, Nateetip; Kengkoom, Kanchana; Charoenphandhu, Narattaphol

    2014-02-01

    Chronic renal impairment can lead to bone deterioration and abnormal bone morphology, but whether hydronephrosis is associated with bone loss remains unclear. Herein, we aimed to use computer-assisted bone histomorphometric technique to investigate microstructural bone changes in Imprinting Control Region (ICR) mice with a spontaneous mutation that was associated with bilateral nonobstructive hydronephrosis (ICR/Mlac-hydro). The results showed that 8-week-old ICR/Mlac-hydro mice manifested decreases in trabecular bone number and thickness, and an increased trabecular separation, thereby leading to a reduction in trabecular bone volume compared with the wild-type mice. Furthermore, histomorphometric parameters related to both bone resorption and formation, that is, eroded surface, osteoclast surface, and osteoblast surface, were much lower in ICR/Mlac-hydro mice than in the wild type. A decrease in moment of inertia was found in ICR/Mlac-hydro mice, indicating a decrease in bone strength. In conclusion, ICR/Mlac-hydro mice exhibited trabecular bone loss, presumably caused by marked decreases in both osteoblast and osteoclast activities, which together reflected abnormally low bone turnover. Thus, this mouse strain appeared to be a valuable model for studying the hydronephrosis-associated bone disease. PMID:24227694

  15. 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

  16. Oral lactoferrin protects against experimental candidiasis in mice

    PubMed Central

    Velliyagounder, Kabilan; Alsaedi, Wijdan; Alabdulmohsen, Waad; Markowitz, Kenneth; Fine, Daniel H.

    2015-01-01

    Aims To determine the role of lactoferrin in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO?/?) mice were compared to wild-type (WT) mice. We also determine the protective role of human lactoferrin in the LFKO?/? mice. Methods and Results Antibiotic treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0.3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO?/?I mice showed a 2 log (P=0.001) higher CFUs of C. albicans in the oral cavity compared to the WTI mice. LFKO?/?I mice given hLF had a 3 log (P=0.001) reduction in CFUs in the oral cavity compared to untreated LFKO?/?I mice. The severity of infection, observed by light microscopy revealed that the tongue of the LFKO?/?I mice showed more white patches compared to WTI and LFKO?/?I+hLF mice. Scanning electron microscopic observation revealed that more filiform papillae were destroyed in LFKO?/?I mice when compared to WTI or LFKO?/?I +hLF mice. Conclusions Human lactoferrin is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Significance and Impact of the Study Human lactoferrin, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral health care products against C. albicans. PMID:25319508

  17. [Antianoxic effects of Dracocephalum tanguticum on brain of mice].

    PubMed

    Hai, P; Zhou, S; Shang, H; Zhao, G

    1997-04-01

    The aqueous extracts i.p. of Dracocephalum tanguticum Maxim (DtM), a Tibetan medicine, prolong sighificantly decapitaion-induced gasping duration in mice and the survival time of mice ligated bilateral carotid (P > 0.01). DtM prolong also the primal gasping in mice after injecting the air into the coccygeal vein (P > 0.01) and the survival time in mice poisoned by Lidocaine (P > 0.05). In addition, DtM is possessed of protecting against the pathologic lession of brain in rats under stimulating high altitude hypoxic condition. The results suggest that DtM has a antianoxic effects on mice. PMID:12572458

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Modeling HIV-1 Mucosal Transmission and Prevention in Humanized Mice.

    PubMed

    Veselinovic, Milena; Charlins, Paige; Akkina, Ramesh

    2016-01-01

    The new generation humanized mice (hu-mice) that permit continuous de novo generation of human hematopoietic cells have led to novel strategies in studying HIV-1 pathogenesis, prevention and therapies. HIV-1 infection of hu-mice results in chronic viremia and CD4+ T cell loss, thus mimicking key aspects of the disease progression. In addition, the new generation hu-mice are permissive for HIV-1 sexual transmission by vaginal and rectal routes thus allowing in vivo efficacy testing of new anti-HIV-1 drugs for prevention. Two leading models are currently being used, namely the hu-HSC mice and the BLT mice. Here we describe the methodology for generating both hu-HSC and BLT mice and their use in the study of HIV-1 transmission and prevention of infection by topical and oral administration of anti-retroviral drugs. Practical aspects of the methodologies are emphasized. PMID:26714714

  3. 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

  4. 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.

  5. 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

  6. The metabolic footprint of aging in mice

    PubMed Central

    Houtkooper, Riekelt H.; Argmann, Carmen; Houten, Sander M.; Cant, Carles; Jeninga, Ellen H.; Andreux, Pnlope A.; Thomas, Charles; Doenlen, Raphal; Schoonjans, Kristina; Auwerx, Johan

    2011-01-01

    Aging is characterized by a general decline in cellular function, which ultimately will affect whole body homeostasis. Although DNA damage and oxidative stress all contribute to aging, metabolic dysfunction is a common hallmark of aging at least in invertebrates. Since a comprehensive overview of metabolic changes in otherwise healthy aging mammals is lacking, we here compared metabolic parameters of young and 2 year old mice. We systemically integrated in vivo phenotyping with gene expression, biochemical analysis, and metabolomics, thereby identifying a distinguishing metabolic footprint of aging. Among the affected pathways in both liver and muscle we found glucose and fatty acid metabolism, and redox homeostasis. These alterations translated in decreased long chain acylcarnitines and increased free fatty acid levels and a marked reduction in various amino acids in the plasma of aged mice. As such, these metabolites serve as biomarkers for aging and healthspan. PMID:22355651

  7. 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-2R?, Cxcl2, TNF?, 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.

  8. Studies of retroviral infection in humanized mice.

    PubMed

    Marsden, Matthew D; Zack, Jerome A

    2015-05-01

    Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been transplanted with human cells and/or tissues. Certain humanized mouse models can support robust infection with human retroviruses including different strains of human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV). These models have provided wide-ranging insights into retroviral biology, including detailed information on primary infection, in vivo replication and pathogenesis, latent/persistent reservoir formation, and novel therapeutic interventions. Here we describe the humanized mouse models that are most commonly utilized to study retroviral infections, and outline some of the important discoveries that these models have produced during several decades of intensive research. PMID:25680625

  9. 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.

  10. Progress on the MICE Tracker Solenoid

    SciTech Connect

    Green, Michael A.; Virostek, Steve P.; Lau, W.; Yang, Stephanie Q.

    2006-06-10

    This report describes the 400 mm warm bore tracker solenoid for the Muon Ionization Cooling Experiment (MICE). The 2.923 m long tracker solenoid module includes the radiation shutter between the end absorber focus coil modules and the tracker as well as the 2.735 m long magnet cryostat vacuum vessel. The 2.554 m long tracker solenoid cold mass consists of two sections, a three-coil spectrometer magnet and a two-coil matching section that matches the uniform field 4 T spectrometer solenoid into the MICE cooling channel. The two tracker magnets are used to provide a uniform magnetic field for the fiber detectors that are used to measure the muon beam emittance at the two ends of the cooling channel. This paper describes the design for the tracker magnet coils and the 4.2 K cryogenic coolers that are used to cool the superconducting magnet. Interfaces between the magnet and the detectors are discussed.

  11. 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

  12. 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

  13. Methylation of dimethyltin in mice and rats.

    PubMed

    Furuhashi, Koichi; Ogawa, Masanori; Suzuki, Yoshihiro; Endo, Yoko; Kim, Yangho; Ichihara, Gaku

    2008-02-01

    Organotins are widely used as stabilizers of polyvinyl chloride and as catalysts or biocides. It is well known that dimethyltin (DMT) is less neurotoxic than trimethyltin (TMT). A Korean worker who was exposed to DMT compounds showed neurological symptoms similar to those of TMT encephalopathy, in association with high levels of both DMT and TMT in the urine and blood. The case suggested the possibility of the methylation of DMT in humans. Here, we investigated whether TMT is detected in the urine of mice and rats exposed only to DMT dichloride (DMTC). Three Slc:ICR mice and three Slc:Wistar rats were placed in individual metabolic cages, and one day later, they were injected intraperitoneally with DMTC (10 mg/kg body weight (wt); 5.4 mgSn/kg body wt; 45.5 micromol/kg body wt) over 4 consecutive days. Twenty-four hour urine samples were collected every evening for 11 consecutive days starting at baseline (before treatment). Speciation analyses of methyltin compounds in urine were performed using a combination of high performance liquid chromatograph-inductively coupled plasma mass spectrometry. High concentrations of DMT and time-dependent increase in TMT concentrations were found in both mice and rats during the 4-day treatment, and their concentrations decreased gradually after the cessation of treatment. The chemical compound of the detected peak was confirmed to be TMT by liquid chromatography-tandem mass spectrometry. Neither DMT nor TMT was detected in the samples collected at baseline. Our results indicate urinary excretion of TMT in mice and rats injected with DMTC, confirming the production of TMT in vivo, probably through methylation of DMT. PMID:18163545

  14. 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.

  15. 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.

  16. 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.

  17. 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-1?, IL-6, IL-10, IL-12p40, IL-13 and TNF? 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

  18. Aggression in mice after p-chloroamphetamine.

    PubMed

    Gianutsos, G; Lal, H

    1975-02-01

    Two or 3 days after a single high-dose (20 mg/Kg) of p-chloroamphetamine (PCA) aggression was reliably observed in male mice. This agression was not produced when the same dose of d-amphetamine was injected or when PCA was injected one hour before testing. However, PCA produced an increase in locomotor activity one hour, but not 24 hours, after injection. PMID:1171509

  19. 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

  20. 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

  1. Cerebral ?-Amyloidosis in Mice Investigated by Ultramicroscopy

    PubMed Central

    Jhrling, Nina; Becker, Klaus; Wegenast-Braun, Bettina M.; Grathwohl, Stefan A.; Jucker, Mathias; Dodt, Hans-Ulrich

    2015-01-01

    Alzheimers disease (AD) is the most common neurodegenerative disorder. AD neuropathology is characterized by intracellular neurofibrillary tangles and extracellular ?-amyloid deposits in the brain. To elucidate the complexity of AD pathogenesis a variety of transgenic mouse models have been generated. An ideal imaging system for monitoring ?-amyloid plaque deposition in the brain of these animals should allow 3D-reconstructions of ?-amyloid plaques via a single scan of an uncropped brain. Ultramicroscopy makes this possible by replacing mechanical slicing in standard histology by optical sectioning. It allows a time efficient analysis of the amyloid plaque distribution in the entire mouse brain with 3D cellular resolution. We herein labeled ?-amyloid deposits in a transgenic mouse model of cerebral ?-amyloidosis (APPPS1 transgenic mice) with two intraperitoneal injections of the amyloid-binding fluorescent dye methoxy-X04. Upon postmortem analysis the total number of ?-amyloid plaques, the ?-amyloid load (volume percent) and the amyloid plaque size distributions were measured in the frontal cortex of two age groups (2.5 versus 7-8.5 month old mice). Applying ultramicroscopy we found in a proof-of-principle study that the number of ?-amyloid plaques increases with age. In our experiments we further observed an increase of large plaques in the older age group of mice. We demonstrate that ultramicroscopy is a fast, and accurate analysis technique for studying ?-amyloid lesions in transgenic mice allowing the 3D staging of ?-amyloid plaque development. This in turn is the basis to study neural network degeneration upon cerebral ?-amyloidosis and to assess A? -targeting therapeutics. PMID:26017149

  2. Cytogenetic analyses of mice exposed to dichloromethane

    SciTech Connect

    Allen, J.; Kligerman, A.; Campbell, J.; Westbrook-Collins, B.; Erexson, G.; Kari, F.; Zeiger, E. )

    1990-01-01

    Chromosome damage was studied in female B6C3F1 mice exposed to dichloromethane (DCM) by subcutaneous or inhalation treatments. No increase in the frequency of either sister chromatid exchanges (SCEs) or chromosome aberrations (CAs) in bone marrow cells was observed after a single subcutaneous injection of 2,500 or 5,000 mg/kg DCM. Inhalation exposure to DCM for 10 days at concentrations of 4,000 or 8,000 ppm resulted in significant increases in frequencies of SCEs in lung cells and peripheral blood lymphocytes, CAs in lung and bone marrow cells, and micronuclei (MN) in peripheral blood erythrocytes. Lung cell CAs and blood erythrocyte MN reached frequencies of approximately two times control levels. Following a 3-month inhalation exposure to 2,000 ppm DCM, mice showed small but significant increases in lung cell SCEs and peripheral blood erythrocyte MN. These findings suggest that genotoxicity may play a role in the carcinogenicity of DCM in the lungs of B6C3F1 female mice.

  3. Intralymphatic Immunotherapy and Vaccination in Mice

    PubMed Central

    Johansen, Pl; Kndig, 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 ?l 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

  4. 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

  5. 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

  6. Wallerian degeneration in ICAM-1-deficient mice.

    PubMed Central

    Vougioukas, V. I.; Roeske, S.; Michel, U.; Brck, W.

    1998-01-01

    Wallerian degeneration of the peripheral nervous system was studied in ICAM-1-deficient mice and compared with the phenomena observed in C57BL wild-type animals. There was a decrease in myelin density in both mice strains 4 and 6 days after transection of the sciatic nerve. The degenerating nerves were invaded by Mac-1-, LFA-1-, and F4/80-positive macrophages; significantly lower numbers of macrophages were present in ICAM-1-deficient nerves. Myelin loss decreased after nerve transection with a more prominent loss in ICAM-1-deficient animals. Schwann cells revealed a much higher myelin load in these animals when compared with wild-type nerves, and there was an increased proliferation of endoneurial cells in ICAM-1-deficient mice. These data indicate that ICAM-1 is involved in macrophage recruitment to injured peripheral nerves as well as in the proliferative and phagocytic response of Schwann cells after peripheral nerve transection. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9422541

  7. 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

  8. Acute toxicity of karlotoxins to mice

    PubMed Central

    Place, Allen R.; Munday, R.; Munday, J.S.

    2015-01-01

    Karlotoxins, polyketide derivatives produced by the dinoflagellate Karlodinium veneficum, are associated with fish kills in temperate estuaries world wide. In this study, the acute effects of 3 pure karlotoxin analogs (KmTx 1, KmTx 3 and KmTx 2) have been examined in mice. Transient lethargy and increased respiratory rates were observed soon after dosing with the karlotoxins by intraperitoneal injection, but no deaths were recorded in animals dosed with KmTx 2 at up to 500 ?g/kg or with KmTx 1 or KmTx 3 at up to 4000 ?g/kg. Animals dosed intraperitoneally with KmTx 1 and KmTx 3 at 4000 ?g/kg showed a pronounced decrease in food and water intake, lasting 34 days after dosing, accompanied by a significant decrease in body weight. After this time, the lost body weight was regained and the behavior and appearance of the mice remained normal throughout the following 10 day observation period. No effects were seen in mice dosed orally with KmTx 1 or KmTx 3 at a dose of 4000 ?g/kg. It is concluded that contamination of seafood if it were to occur with these karlotoxins is unlikely to pose a major risk of acute intoxication in consumers. PMID:25150200

  9. Acute toxicity of karlotoxins to mice.

    PubMed

    Place, Allen R; Munday, R; Munday, J S

    2014-11-01

    Karlotoxins, polyketide derivatives produced by the dinoflagellate Karlodinium veneficum, are associated with fish kills in temperate estuaries world-wide. In this study, the acute effects of 3 pure karlotoxin analogs (KmTx 1, KmTx 3 and KmTx 2) have been examined in mice. Transient lethargy and increased respiratory rates were observed soon after dosing with the karlotoxins by intraperitoneal injection, but no deaths were recorded in animals dosed with KmTx 2 at up to 500 ?g/kg or with KmTx 1 or KmTx 3 at up to 4000 ?g/kg. Animals dosed intraperitoneally with KmTx 1 and KmTx 3 at 4000 ?g/kg showed a pronounced decrease in food and water intake, lasting 3-4 days after dosing, accompanied by a significant decrease in body weight. After this time, the lost body weight was regained and the behavior and appearance of the mice remained normal throughout the following 10-day observation period. No effects were seen in mice dosed orally with KmTx 1 or KmTx 3 at a dose of 4000 ?g/kg. It is concluded that contamination of seafood if it were to occur with these karlotoxins is unlikely to pose a major risk of acute intoxication in consumers. PMID:25150200

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Connective tissue alterations in Fkbp10?/? mice

    PubMed Central

    Lietman, Caressa D.; Rajagopal, Abbhirami; Homan, Erica P.; Munivez, Elda; Jiang, Ming-Ming; Bertin, Terry K.; Chen, Yuqing; Hicks, John; Weis, MaryAnn; Eyre, David; Lee, Brendan; Krakow, Deborah

    2014-01-01

    Osteogenesis imperfecta (OI) is an inherited brittle bone disorder characterized by bone fragility and low bone mass. Loss of function mutations in FK506-binding protein 10 (FKBP10), encoding the FKBP65 protein, result in recessive OI and Bruck syndrome, of which the latter is additionally characterized by joint contractures. FKBP65 is thought to act as a collagen chaperone, but it is unknown how loss of FKBP65 affects collagen synthesis and extracellular matrix formation. We evaluated the developmental and postnatal expression of Fkbp10 and analyzed the consequences of its generalized loss of function. Fkbp10 is expressed at low levels in E13.5 mouse embryos, particularly in skeletal tissues, and steadily increases through E17.5 with expression in not only skeletal tissues, but also in visceral tissues. Postnatally, expression is limited to developing bone and ligaments. In contrast to humans, with complete loss of function mutations, Fkbp10?/? mice do not survive birth, and embryos present with growth delay and tissue fragility. Type I calvarial collagen isolated from these mice showed reduced stable crosslink formation at telopeptide lysines. Furthermore, Fkbp10?/? mouse embryonic fibroblasts show retention of procollagen in the cell layer and associated dilated endoplasmic reticulum. These data suggest a requirement for FKBP65 function during embryonic connective tissue development in mice, but the restricted expression postnatally in bone, ligaments and tendons correlates with the bone fragility and contracture phenotype in humans. PMID:24777781

  16. Connective tissue alterations in Fkbp10-/- mice.

    PubMed

    Lietman, Caressa D; Rajagopal, Abbhirami; Homan, Erica P; Munivez, Elda; Jiang, Ming-Ming; Bertin, Terry K; Chen, Yuqing; Hicks, John; Weis, MaryAnn; Eyre, David; Lee, Brendan; Krakow, Deborah

    2014-09-15

    Osteogenesis imperfecta (OI) is an inherited brittle bone disorder characterized by bone fragility and low bone mass. Loss of function mutations in FK506-binding protein 10 (FKBP10), encoding the FKBP65 protein, result in recessive OI and Bruck syndrome, of which the latter is additionally characterized by joint contractures. FKBP65 is thought to act as a collagen chaperone, but it is unknown how loss of FKBP65 affects collagen synthesis and extracellular matrix formation. We evaluated the developmental and postnatal expression of Fkbp10 and analyzed the consequences of its generalized loss of function. Fkbp10 is expressed at low levels in E13.5 mouse embryos, particularly in skeletal tissues, and steadily increases through E17.5 with expression in not only skeletal tissues, but also in visceral tissues. Postnatally, expression is limited to developing bone and ligaments. In contrast to humans, with complete loss of function mutations, Fkbp10(-/-) mice do not survive birth, and embryos present with growth delay and tissue fragility. Type I calvarial collagen isolated from these mice showed reduced stable crosslink formation at telopeptide lysines. Furthermore, Fkbp10(-/-) mouse embryonic fibroblasts show retention of procollagen in the cell layer and associated dilated endoplasmic reticulum. These data suggest a requirement for FKBP65 function during embryonic connective tissue development in mice, but the restricted expression postnatally in bone, ligaments and tendons correlates with the bone fragility and contracture phenotype in humans. PMID:24777781

  17. Effect of methamphetamine on male mice fertility.

    PubMed

    Yamamoto, Y; Yamamoto, K; Hayase, T

    1999-10-01

    The effect of methamphetamine (MAMP) on the ability of males to mate with females and to impregnate them was examined in 8-week-old ICR mice. Male mice that had been administered an intraperitoneal injection of MAMP (15 mg/kg, 7.5 mg/kg, or 3.75 mg/kg) or saline were housed with females 24 or 48 hours later. The vaginal plugs were checked, and the number of births was counted. The effect of MAMP on sperm motility and the serum testosterone (TS) concentration was also examined. Methamphetamine was observed to have harmful effects only at the highest dose level. In the mice housed 24 hours after the injection of 15 mg/kg MAMP, the increase in the cumulative number of vaginal plugs lagged, and the total number of vaginal plugs decreased significantly. A significant decrease was also observed in the total number of births. Methamphetamine, at a dose of 15 mg/kg, decreased sperm motility. The TS concentration decreased initially, then increased. PMID:10533332

  18. Hepatotoxic effects of mycotoxin combinations in mice.

    PubMed

    Sun, Lv-Hui; Lei, Ming-yan; Zhang, Ni-Ya; Zhao, Ling; Krumm, Christopher Steven; Qi, De-Sheng

    2014-12-01

    This study was performed to assess the individual and combined toxic effects of aflatoxin B1 (AFB1), zearalenone (ZEA) and deoxynivalenol (DON) within the liver of mice. A total of 56 4-week-old weanling female mice were divided into seven groups (n?=?8). For 2 weeks, each group received an oral administration of either solvent (control), AFB1, ZEA, DON, AFB1?+?ZEA, AFB1?+?DON or ZEA?+?DON per day. The results showed that AFB1, ZEA and DON induced liver injury, indicated by elevated relative liver weight, activities of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), as well as decreased albumin (ALB) and/or total protein (TP) concentration in the serum. These mycotoxins also decreased hepatic total antioxidant capacity (T-AOC), and/or increased the concentration of malondialdehyde (MDA). Moreover, AFB1?+?DON displayed synergistic effects, while AFB1?+?ZEA displayed antagonistic effects on those parameters previously described. Furthermore, the apoptotic potential was demonstrated associated with an upregulation of the apoptotic genes Caspase-3 and Bax, along with a downregulation of the antiapoptotic gene Bcl-2 in liver. In conclusion, this study provides a better understanding of the toxic effects of AFB1, ZEA, DON, alone or in combinations on the liver of mice, which could contribute to the risk assessment of these mycotoxins in food and feed. PMID:25445755

  19. Transgenic Mice for cGMP Imaging

    PubMed Central

    Thunemann, Martin; Wen, Lai; Hillenbrand, Matthias; Vachaviolos, Angelos; Feil, Susanne; Ott, Thomas; Han, Xiaoxing; Fukumura, Dai; Jain, Rakesh K.; Russwurm, Michael; de Wit, Cor; Feil, Robert

    2014-01-01

    Rationale Cyclic GMP (cGMP) is an important intracellular signaling molecule in the cardiovascular system, but its spatiotemporal dynamics in vivo is largely unknown. Objective To generate and characterize transgenic mice expressing the fluorescence resonance energy transferbased ratiometric cGMP sensor, cGMP indicator with an EC50 of 500 nmol/L (cGi500), in cardiovascular tissues. Methods and Results Mouse lines with smooth musclespecific or ubiquitous expression of cGi500 were generated by random transgenesis using an SM22? promoter fragment or by targeted integration of a Cre recombinaseactivatable expression cassette driven by the cytomegalovirus early enhancer/chicken ?-actin/?-globin promoter into the Rosa26 locus, respectively. Primary smooth muscle cells isolated from aorta, bladder, and colon of cGi500 mice showed strong sensor fluorescence. Basal cGMP concentrations were <100 nmol/L, whereas stimulation with cGMP-elevating agents such as 2-(N,N-diethylamino)-diazenolate-2-oxide diethylammonium salt (DEA/NO) or the natriuretic peptides, atrial natriuretic peptide, and C-type natriuretic peptide evoked fluorescence resonance energy transfer changes corresponding to cGMP peak concentrations of ?3 mol/L. However, different types of smooth muscle cells had different sensitivities of their cGMP responses to DEA/NO, atrial natriuretic peptide, and C-type natriuretic peptide. Robust nitric oxideinduced cGMP transients with peak concentrations of ?1 to >3 mol/L could also be monitored in blood vessels of the isolated retina and in the cremaster microcirculation of anesthetized mice. Moreover, with the use of a dorsal skinfold chamber model and multiphoton fluorescence resonance energy transfer microscopy, nitric oxidestimulated vascular cGMP signals associated with vasodilation were detected in vivo in an acutely untouched preparation. Conclusions These cGi500 transgenic mice permit the visualization of cardiovascular cGMP signals in live cells, tissues, and mice under normal and pathological conditions or during pharmacotherapy with cGMP-elevating drugs. PMID:23801067

  20. IL-4 Knock Out Mice Display Anxiety-Like Behavior.

    PubMed

    Moon, Morgan L; Joesting, Jennifer J; Blevins, Neil A; Lawson, Marcus A; Gainey, Stephen J; Towers, Albert E; McNeil, Leslie K; Freund, Gregory G

    2015-07-01

    Inflammation is a recognized antecedent and coincident factor when examining the biology of anxiety. Little is known, however, about how reductions in endogenous anti-inflammatory mediators impact anxiety. Therefore, mood- cognition- and anxiety-associated/like behaviors were examined in IL-4 knock out (KO) mice and wild-type (WT) mice. In comparison to WT mice, IL-4 KO mice demonstrated decreased burrowing and increased social exploration. No differences were seen in forced swim or saccharine preference testing. IL-4 KO mice had similar performance to WT mice in the Morris water maze and during object location and novel object recognition. In the elevated zero-maze, IL-4 KO mice, in comparison to WT mice, demonstrated anxiety-like behavior. Anxiety-like behavior in IL-4 KO mice was not observed, however, during open-field testing. Taken together, these data indicate that IL-4 KO mice display state, but not trait, anxiety suggesting that reductions in endogenous anti-inflammatory bioactives can engender subtypes of anxiety. PMID:25772794

  1. Genetic impacts of Anacapa deer mice reintroductions following rat eradication.

    PubMed

    Ozer, Fusun; Gellerman, Holly; Ashley, Mary V

    2011-09-01

    The Anacapa deer mouse is an endemic subspecies that inhabits Anacapa Island, part of Channel Islands National Park, California. We used mitochondrial DNA cytochrome c oxidase subunit II gene (COII) and 10 microsatellite loci to evaluate the levels of genetic differentiation and variation in ~1400 Anacapa deer mice sampled before and for 4 years after a black rat (Rattus rattus) eradication campaign that included trapping, captive holding and reintroduction of deer mice. Both mitochondrial and microsatellite analyses indicated significant differentiation between Anacapa deer mice and mainland mice, and genetic variability of mainland mice was significantly higher than Anacapa mice even prior to reintroduction. Bayesian cluster analysis and Principal Coordinates Analysis indicated that East, Middle and West Anacapa mice were genetically differentiated from each other, but translocation of mice among islands resulted in the East population becoming less distinct as a result of management. Levels of heterozygosity were similar before and after management. However, numerous private alleles in the founder populations were not observed after reintroduction and shifts in allele frequencies occurred, indicating that the reintroduced populations experienced substantial genetic drift. Surprisingly, two mitochondrial haplotypes observed in an earlier study of Anacapa deer mice were lost in the 20 years prior to the rat eradication program, leaving only a single haplotype in Anacapa deer mice. This study demonstrates how genetic monitoring can help to understand the re-establishment of endemic species after the eradication of invasive species and to evaluate the effectiveness of the management strategies employed. PMID:21711403

  2. Distribution of manganese and other biometals in flatiron mice.

    PubMed

    Seo, Young Ah; Elkhader, Jamal A; Wessling-Resnick, Marianne

    2016-02-01

    Flatiron (ffe) mice display features of "ferroportin disease" or Type IV hereditary hemochromatosis. While it is known that both Fe and Mn metabolism are impaired in flatiron mice, the effects of ferroportin (Fpn) deficiency on physiological distribution of these and other biometals is unknown. We hypothesized that Fe, Mn, Zn and/or Cu distribution would be altered in ffe/+ compared to wild-type (+/+) mice. ICP-MS analysis showed that Mn, Zn and Cu levels were significantly reduced in femurs from ffe/+ mice. Bone deposits reflect metal accumulation, therefore these data indicate that Mn, Zn and Cu metabolism are affected by Fpn deficiency. The observations that muscle Cu, lung Mn, and kidney Cu and Zn levels were reduced in ffe/+ mice support the idea that metal metabolism is impaired. While all four biometals appeared to accumulate in brains of flatiron mice, significant gender effects were observed for Mn and Zn levels in male ffe/+ mice. Metals were higher in olfactory bulbs of ffe/+ mice regardless of gender. To further study brain metal distribution, (54)MnCl2 was administered by intravenous injection and total brain (54)Mn was measured over time. At 72h, (54)Mn was significantly greater in brains of ffe/+ mice compared to +/+ mice while blood (54)Mn was cleared to the same levels by 24h. Taken together, these results indicate that Fpn deficiency decreases Mn trafficking out of the brain, alters body Fe, Mn, Zn and Cu levels, and promotes metal accumulation in olfactory bulbs. PMID:26693922

  3. 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

  4. 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.

  5. 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.

  6. Enterotropic mouse hepatitis virus infection in nude mice.

    PubMed

    Barthold, S W; Smith, A L; Povar, M L

    1985-12-01

    The cause of emaciation and diarrhea in athymic nude mice was found to be hyperplastic typhlocolitis resulting from infection with enterotropic mouse hepatitis virus (MHV). The disease was reproduced in experimentally-inoculated nude mice using intestinal homogenates from affected mice and cell culture-derived virus. Material derived from an experimental mouse was passed into neonatal Swiss mice and caused acute typhlocolitis. Virus failed to grow in NCTC-1469 cells and 17Cl-1 cells, which are normally permissive for MHV, but grew to low titer in a mouse rectal carcinoma cell line, CMT 93. These results show that an enterotropic strain of MHV can cause chronic enteric disease in athymic nude mice. The pattern of infection differs markedly from the more common MHV wasting syndrome in nude mice caused by non-enteric strains of MHV. PMID:3005764

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. Diet-induced obese mice retain endogenous leptin action.

    PubMed

    Ottaway, Nickki; Mahbod, Parinaz; Rivero, Belen; Norman, Lee Ann; Gertler, Arieh; D'Alessio, David A; Perez-Tilve, Diego

    2015-06-01

    Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice. PMID:25980347

  12. 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

  13. Humoral intestinal immunity against Encephalitozoon cuniculi (Microsporidia) infection in mice.

    PubMed

    Sak, Bohumil; Ditrich, Oleg

    2005-05-01

    Three strains of mice, BALB/c, IL-12 knock-out (KO) and INF-gamma knock-out, were chosen as an experimental model for the study of intestinal immunity induction against Encephalitozoon cuniculi Levaditi, Nicolau et Schoen, 1923 infection. Mice were infected perorally with 10(7) spores and re-infected with the same dose 70 days after the first infection. The anti-E. cuniculi IgA, IgG and IgM responses in sera and extracts of stool samples were determined by ELISA. Results have shown specific antibody production in the sera and intestinal secretions of all three strains of mice induced orally by E. ciniculi spores. BALB/c mice developed a stronger humoral immune response than IL-12 KO mice. The lowest antibody response developed in INF-gamma KO mice that succumbed to the infection within 28 days post infection. PMID:16004375

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

    PubMed Central

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

    2012-01-01

    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 2224% nt (1518% aa) positions from the laboratory mouse MNVs and at 2022% nt (1314% 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

  15. 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

  16. 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

  17. 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

  18. Acute toxicity of taxine in mice and rats.

    PubMed

    Tekol, Y

    1991-08-01

    The acute toxicity of taxine isolated from leaves of yew trees was determined in mice and rats. The drug was used as the sulphate salt. The following LD50 values (mg/kg) and 95% confidence limits were found: mice po 19.72 (16.84-23.09); mice ip 21.88 (19.66-24.35); rats sc 20.18 (18.35-22.20). PMID:1897127

  19. Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

    PubMed Central

    Imai, Saki; Kano, Makoto; Nonoyama, Keiko; Ebihara, Shizufumi

    2013-01-01

    We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system. PMID:23472206

  20. 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

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

    PubMed

    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 ? or ? (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

  2. 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

  3. Vocal ontogeny in neotropical singing mice (Scotinomys).

    PubMed

    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

  4. Neurobiological changes by cytotoxic agents in mice.

    PubMed

    Seigers, R; Loos, M; Van Tellingen, O; Boogerd, W; Smit, A B; Schagen, S B

    2016-02-15

    Cognitive deficit is a frequently reported side-effect of adjuvant chemotherapy. A large number of animal studies has been performed to examine the neurobiological mechanisms underlying this phenomenon, however, definite conclusions from these studies are restricted due to differences in experimental set-up. We systematically investigated the effects of 6 cytotoxic agents on various neurobiological parameters. C57Bl/6J mice were treated with cyclophosphamide, docetaxel, doxorubicin, 5-fluorouracil, methotrexate, or topotecan. The animals were sacrificed 3 or 15 weeks after treatment and the effect on neurogenesis, blood vessel density, and neuroinflammation was analyzed using immunohistochemistry. None of the cytostatic agents tested affected neurogenesis (cell survival or cell proliferation). Blood vessel density was increased in the hippocampus and prefrontal cortex 3 weeks after treatment with docetaxel and doxorubicin compared with control animals. A decrease in the number of microglial cells was observed in the prefrontal cortex after treatment with cyclophosphamide, docetaxel, 5-FU, and topotecan compared with control mice. The observed decrease in microglia cells is indicative of inflammation that occurred after treatment. Overall, the magnitude of the effects was relatively modest. Therefore, we conducted a similar study with topotecan in Abcg2;Abcb1a/b knock out and wildtype FVB mice. Animals were sacrificed 3 weeks after treatment and no notable effect was seen in hippocampal cell differentiation (DCX), microglia activation, or blood vessel density. Perhaps the FVB strain is more resistant to the neurotoxic effects of topotecan which makes this not the correct model to study the mechanism of chemotherapy-induced cognitive impairment. PMID:26602283

  5. 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

  6. Polydactyly in mice lacking HDAC9/HDRP.

    PubMed

    Morrison, Brad E; D'Mello, Santosh R

    2008-08-01

    Mice lacking histone deacetylase 9 (HDAC9) and its truncated variant, HDRP, exhibit post-axial polydactyly that manifests as an extra big toe on the right hind foot. Polydactyly in HDAC9/ HDRP knockout mice occurs with incomplete penetrance and affects both genders similarly. Because polydactyly can result from overactivity of sonic hedgehog (Shh) signaling, we investigated whether HDRP acted as a negative regulator of the Shh pathway. We find that Gli1, a transcription factor and downstream mediator of Shh signaling, is expressed at substantially higher levels in the feet of perinatal HDAC9/ HDRP-/- mice as compared with wild-type littermates. To more directly examine whether HDRP negatively-regulates Shh signaling we utilized cell lines that express components of the Shh pathway and that respond to the Shh agonist purmorphamine. We find that purmorphamine-mediated stimulation of Gli1 in the NIH 3T3 and HT22 cell lines is inhibited by the expression of HDRP. In HT22 cells, purmorphamine treatment leads to an increase in the rate of cell proliferation, which is also inhibited by HDRP. This inhibitory effect of HDRP on purmorphamine-mediated cell proliferation was also observed in primary cultures of glial cells. Although the mechanism by which it inhibits Gli1 induction and cell proliferation by purmorphamine is not clear, HDRP localizes to the nucleus suggesting it acts just upstream of Gli3 activation in the signaling cascade activated by Shh. Taken together our results suggest that HDRP acts as a negative regulator of the Shh pathway and that the absence of HDRP results in hyper-activation of this pathway resulting in polydactyly. PMID:18480421

  7. Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q.

    PubMed

    Ghebrehiwet, B; Lim, B L; Peerschke, E I; Willis, A C; Reid, K B

    1994-06-01

    This work describes the functional characterization, cDNA cloning, and expression of a novel cell surface protein. This protein designated gC1q-R, was first isolated from Raji cells and was found to bind to the globular "heads" of C1q molecules, at physiological ionic strength, and also to inhibit complement-mediated lysis of sheep erythrocytes by human serum. The NH2-terminal amino acid sequence of the first 24 residues of the C1q-binding protein was determined and this information allowed the synthesis of two degenerate polymerase chain reaction primers for use in the preparation of a probe in the screening of a B cell cDNA library. The cDNA isolated, using this probe, was found to encode a pre-pro protein of 282 residues. The NH2 terminus of the protein isolated from Raji cells started at residue 74 of the predicted pre-pro sequence. The cDNA sequence shows that the purified protein has three potential N-glycosylation residues and is a highly charged, acidic molecule. Hence, its binding to C1q may be primarily but not exclusively due to ionic interactions. The "mature" protein, corresponding to amino acid residues 74-282 of the predicted pre-pro sequence, was overexpressed in Escherichia coli and was purified to homogeneity. This recombinant protein was also able to inhibit the complement-mediated lysis of sheep erythrocytes by human serum and was shown to be a tetramer by gel filtration in nondissociating conditions. Northern blot and RT-PCR studies showed that the C1q-binding protein is expressed at high levels in Raji and Daudi cell lines, at moderate levels in U937, Molt-4, and HepG2 cell lines, and at a very low level in the HL60 cell line. However, it is not expressed in the K562 cell line. Comparison of gC1q-R NH2-terminal sequence with that of the receptor for the collagen-like domain of C1q (cC1q-R) showed no similarity. Furthermore, antibodies to gC1q-R or an 18-amino acid residue-long NH2-terminal synthetic gC1q-R peptide did not cross-react with antibodies to cC1q-R. Anti-gC1q-R immunoblotted a 33-kD Raji cell membrane protein, whereas anti cC1q-R recognized a molecule of approximately 60 kD. The NH2-terminal sequence of gC1g-R appears to be displayed extracellularly since anti-gC1g-R peptide reacted with surface molecules on lymphocytes, polymorphonuclear leukocytes, and platelets, as assessed by flow cytometric and confocal laser scanning microscopic analyses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8195709

  8. Measurement of Sulfur Isotopic Composition (?34S) by Multiple-Collector Thermal Ionization Mass Spectrometry (MC-TIMS) Using a 33S/36S Double Spike

    NASA Astrophysics Data System (ADS)

    Mann, J. L.; Kelly, W. R.

    2006-05-01

    A new analytical technique for the determination of ?34S will be described. The technique is based on the production of singularly charged arsenic sulfide molecular ions (AsS+) by thermal ionization using silica gel as an emitter and combines multiple-collector thermal ionization mass spectrometry (MC-TIMS) with a 33S/36S double spike to correct instrumental fractionation. Because the double spike is added to the sample before chemical processing, both the isotopic composition and sulfur concentration are measured simultaneously. The accuracy and precision of the double spike technique is comparable to or better than modern gas source mass spectrometry, but requires about a factor of 10 less sample. ?33S effects can be determined directly in an unspiked sample without any assumptions about the value of k (mass dependent fractionation factor) which is currently required by gas source mass spectrometry. Three international sulfur standards (IAEA-S-1, IAEA-S-2, and IAEA-S-3) were measured to evaluate the precision and accuracy of the new technique and to evaluate the consensus values for these standards. Two different double spike preparations were used. The ?34S values (reported relative to Vienna Canyon Diablo Troilite (VCDT), (?34S () = 34S/32S)sample/(34S/32S)VCDT - 1) x 1000]), 34S/32SVCDT = 0.0441626) determined were -0.32 0.04 (1?, n=4) and -0.31 0.13 (1?, n=8) for IAEA-S-1, 22.65 0.04 (1?, n=7) and 22.60 0.06 (1?, n=5) for IAEA- S-2, and -32.47 0.07 (1?, n=8) for IAEA-S-3. The amount of natural sample used for these analyses ranged from 0.40 ?moles to 2.35 ?moles. Each standard showed less than 0.5 variability (IAEA-S-1 < 0.4, IAEA-S-2 < 0.2, and IAEA-S-3 < 0.2). Our values for S-1 and S-2 are in excellent agreement with the consensus values and the values reported by other laboratories using both SF6 and SO2. Our value for S-3 differs statistically from the Institute for Reference Materials and Measurement (IRMM) value and is slightly lower than the currently accepted consensus value (-32.3). Because the technique is based on thermal ionization of AsS+, and As is mononuclidic, corrections for interferences or for scale contraction/expansion are not required. The availability of MC-TIMS instruments in laboratories around the world makes this technique immediately available to a much larger scientific community who require highly accurate and precise measurements of sulfur.

  9. Brain schistosomiasis in mice experimentally infected with Schistosoma mansoni.

    PubMed

    Lambertucci, Jos Roberto; Fidelis, Thiago Andr; Pereira, Thiago Almeida; Coelho, Paulo Marcos Zech; Araujo, Neuza; Souza, Mrcia Maria de; Brasileiro, Geraldo; Pereira, Fausto Edmundo Lima; Antunes, Carlos Mauricio

    2014-02-12

    Introduction Human neuroschistosomiasis has been reported in the literature, but the possibility of modeling neuroschistosomiasis in mice is controversial. Methods In two research laboratories in Brazil that maintain the Schistosoma mansoni life cycle in rodents, two mice developed signs of brain disease (hemiplegia and spinning), and both were autopsied. Results S. mansoni eggs, both with and without granuloma formation, were observed in the brain and meninges of both mice by optical microscopy. Conclusions This is the first description of eggs in the brains of symptomatic mice that were experimentally infected with S. mansoni. An investigation of experimental neuroschistosomiasis is now feasible. PMID:24553801

  10. Assessing cervical dislocation as a humane euthanasia method in mice.

    PubMed

    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

    2012-05-01

    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

  11. 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

  12. 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

  13. 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.

  14. Experimental Pneumocystis carinii pneumonia in different strains of cortisonized mice.

    PubMed Central

    Walzer, P D; Powell, R D; Yoneda, K

    1979-01-01

    Pneumocystis carinii pneumonia was produced in eight different strains of mice by the administration of corticosteroids, low (8%)-protein diet, and tetracycline in the drinking water. Heavier degrees of P. carinii infection were most consistently found in C3H/HeN mice; intermediate levels occurred in BALB/c AnN, C57BL/6N, B10.A(2R), AKR/J, and Swiss Webster mice; lighter degrees were found in DBA/2N and DBA/IJ mice. Histopathologically, P. carinii organisms were morphologically indistinguishable from human and rat P. carinii, and elicited a predominantly mononuclear response that was similar among the various mouse strains. The optimal cortisone acetate regimen was 1 mg injected subcutaneously twice weekly. Higher doses shortened the life span of the mice, presumably by inducing overwhelming bacterial infection. This problem occurred not only in different strains of mice, but also in the same strain of mice obtained from different breeders. Thus, cortisonized mice should be useful in the study of experimental P. carinii infection. Success of this model depends on the corticosteroid dose, as well as the strain, source, general health, and preexisting microbial flora of the mice chosen for study. Images PMID:313907

  15. 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

  16. Isavuconazole Therapy Protects Immunosuppressed Mice from Mucormycosis

    PubMed Central

    Luo, Guanpingsheng; Gebremariam, Teclegiorgis; Lee, Hongkyu; Edwards, John E.; Kovanda, Laura

    2014-01-01

    We studied the in vitro and in vivo efficacies of the investigational drug isavuconazole against mucormycosis due to Rhizopus delemar. Isavuconazole was effective, with MIC and minimal fungicidal concentration (MFC) values ranging between 0.125 and 1.00 ?g/ml. A high dose of isavuconazole prolonged the survival time and lowered the tissue fungal burden of cyclophosphamide/cortisone acetate-treated mice infected with R. delemar and was as effective as a high-dose liposomal amphotericin B treatment. These results support the further development of this azole against mucormycosis. PMID:24492363

  17. Humanized Mice as Preclinical Models in Transplantation.

    PubMed

    Safinia, N; Becker, P D; Vaikunthanathan, T; Xiao, F; Lechler, R; Lombardi, G

    2016-01-01

    Animal models have been instrumental in our understanding of the mechanisms of rejection and the testing of novel treatment options in the context of transplantation. We have now entered an exciting era with research on humanized mice driving advances in translational studies and in our understanding of the function of human cells in response to pathogens and cancer as well as the recognition of human allogeneic tissues in vivo. In this chapter we provide a historical overview of humanized mouse models of transplantation to date, outlining the distinct strains and share our experiences in the study of human transplantation immunology. PMID:26530801

  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. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. Circadian Dysfunction Induces Leptin Resistance in Mice.

    PubMed

    Kettner, Nicole M; Mayo, Sara A; Hua, Jack; Lee, Choogon; Moore, David D; Fu, Loning

    2015-09-01

    Circadian disruption is associated with obesity, implicating the central clock in body weight control. Our comprehensive screen of wild-type and three circadian mutant mouse models, with or without chronic jet lag, shows that distinct genetic and physiologic interventions differentially disrupt overall energy homeostasis and Leptin signaling. We found that BMAL1/CLOCK generates circadian rhythm of C/EBP?-mediated leptin transcription in adipose. Per and Cry mutant mice show similar disruption of peripheral clock and deregulation of leptin in fat, but opposite body weight and composition phenotypes that correlate with their distinct patterns of POMC neuron deregulation in the arcuate nucleus. Chronic jet lag is sufficient to disrupt the endogenous adipose clock and also induce central Leptin resistance in wild-type mice. Thus, coupling of the central and peripheral clocks controls Leptin endocrine feedback homeostasis. We propose that Leptin resistance, a hallmark of obesity in humans, plays a key role in circadian dysfunction-induced obesity and metabolic syndromes. PMID:26166747

  8. 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.

  9. Dedicated low-field MRI in mice

    NASA Astrophysics Data System (ADS)

    Choquet, P.; Breton, E.; Goetz, C.; Marin, C.; Constantinesco, A.

    2009-09-01

    The rationale of this work is to point out the relevance of in vivo MR images of mice obtained using a dedicated low-field system. For this purpose a small 0.1 T water-cooled electro-magnet and solenoidal radio frequency (RF) transmit-receive coils were used. All MR images were acquired in three-dimensional (3D) mode. An isolation cell was designed allowing easy placement of the RF coils and simple delivery of gaseous anesthesia as well as warming of the animal. Images with and without contrast agent were obtained in total acquisition times on the order of half an hour to four hours on normal mice as well as on animals bearing tumors. Typical in plane pixel dimensions range from 200 200 to 500 500 m2 with slice thicknesses ranging between 0.65 and 1.50 mm. This work shows that, besides light installation and low cost, dedicated low-field MR systems are suitable for small rodents imaging, opening this technique even to small research units.

  10. Radioprotective Effects of Gallic Acid in Mice

    PubMed Central

    Nair, Gopakumar Gopinathan

    2013-01-01

    Radioprotecting ability of the natural polyphenol, gallic acid (3,4,5-trihydroxybenzoic acid, GA), was investigated in Swiss albino mice. Oral administration of GA (100?mg/kg body weight), one hour prior to whole body gamma radiation exposure (28?Gy; 6 animals/group), reduced the radiation-induced cellular DNA damage in mouse peripheral blood leukocytes, bone marrow cells, and spleenocytes as revealed by comet assay. The GA administration also prevented the radiation-induced decrease in the levels of the antioxidant enzyme, glutathione peroxidise (GPx), and nonprotein thiol glutathione (GSH) and inhibited the peroxidation of membrane lipids in these animals. Exposure of mice to whole body gamma radiation also caused the formation of micronuclei in blood reticulocytes and chromosomal aberrations in bone marrow cells, and the administration of GA resulted in the inhibition of micronucleus formation and chromosomal aberrations. In irradiated animals, administration of GA elicited an enhancement in the rate of DNA repair process and a significant increase in endogenous spleen colony formation. The administration of GA also prevented the radiation-induced weight loss and mortality in animals (10 animals/group) exposed to lethal dose (10 Gy) of gamma radiation. (For every experiment unirradiated animals without GA administration were taken as normal control; specific dose (Gy) irradiated animals without GA administration serve as radiation control; and unirradiated GA treated animals were taken as drug alone control). PMID:24069607

  11. Teratogenicity of secalonic acid D in mice.

    PubMed

    Reddy, C S; Reddy, R V; Hayes, A W; Ciegler, A

    1981-01-01

    Teratogenicity and fetotoxicity of secalonic acid D, a toxic fungal metabolite produced by Penicillium oxalicum, were investigated with pregnant CD1 mice. The compound was administered ip on d 7-15 of pregnancy. A dose-dependent reduction in weight gain of mothers receiving all doses of secalonic acid D and an increase in resorptions of implanted embryos of dams treated with more than 5 mg/kg secalonic acid D occurred. The latter effect was nearly 100% at 15 or 9 mg/kg given in NaHCO3 with or without dimethyl sulfoxide (DMSO), respectively. A corresponding decrease in the percent of live fetuses and a decrease in the average fetal body weight on d 19 of pregnancy also occurred. Multiple gross, skeletal, and visceral anomalies were noted in fetuses born to mothers receiving 10 mg/kg or more in NaHCO3 containing DMSO. In NaHCO3 alone, the minimum teratogenic dose was 6 mg/kg. Major malformations included cleft palate, cleft lip, open eyelids, missing phalangeal ossification centers, and shortened mandibles. The results indicated that secalonic acid D is embryocidal and teratogenic as well as fetotoxic when given to female CD1 mice during pregnancy. PMID:7288897

  12. Surgical Stress Delays Prostate Involution in Mice

    PubMed Central

    Hassan, Sazzad; Karpova, Yelena; Flores, Anabel; DAgostino, Ralph; Kulik, George

    2013-01-01

    Androgens control growth of prostate epithelial cells and androgen deprivation induces apoptosis, leading to prostate involution. We investigated the effects of surgical stress on prostate involution induced by androgen ablation and determined the underlying mechanisms. Androgen ablation in mice was induced by surgical castration and administration of the anti-androgenic drugs bicalutamide and MDV3100. Surgical stress was induced by sham castration under isoflurane anesthesia. Surgical stress delayed apoptosis and prostate involution induced by anti-androgenic drugs. These effects of stress were prevented by administering the selective beta2-adrenoreceptor antagonist ICI118,551 and were also blocked in BAD3SA/WT mice expressing phosphorylation-deficient mutant BAD3SA. These results indicate that apoptosis and prostate involution in response to androgen ablation therapy could be delayed by surgical stress via the beta2-adrenoreceptor/BAD signaling pathway. Thus, surgery could interfere with androgen ablation therapy, whereas administration of beta2-adrenoreceptor antagonists may enhance its efficacy. PMID:24223137

  13. Lung adenocarcinomas: comparison between mice and men.

    PubMed

    Popper, Helmut H

    2015-01-01

    A few human tumor types have been modeled in mice using genetic or chemical tools. The final goal of these efforts is to establish models that mimic not only the location and cellular origin of human cancers but also their genetic aberrations and morphologic appearances. The latter has been neglected by most investigators, and comparative histopathology of human versus mouse cancers is not readily available. This issue is exacerbated by the fact that some human malignancies comprise a whole spectrum of cancer subtypes that differ molecularly and morphologically. Lung cancer is a paradigm that appears not only as non-small cell and small-cell lung cancer but comprises a plethora of subtypes with distinct morphologic features. This review discusses species-specific and common morphological features of non-small cell lung cancer in mice and humans. Potential inconsistencies and the need for refined genetic tools are discussed in the context of a comparative analysis between commonly employed RAS-induced mouse tumors and human lung cancers. PMID:25636463

  14. Oestrogen sulfotransferase ablation sensitizes mice to sepsis.

    PubMed

    Chai, Xiaojuan; Guo, Yan; Jiang, Mengxi; Hu, Bingfang; Li, Zhigang; Fan, Jie; Deng, Meihong; Billiar, Timothy R; Kucera, Heidi R; 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 oestrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the caecal ligation and puncture (CLP) and lipopolysaccharide models of sepsis induce the expression of EST and compromise the activity of oestrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised oestrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes oestrogen deactivation and sensitizes mice to CLP-induced inflammatory response. The induction of EST by sepsis is NF-?B dependent and EST is a NF-?B-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

  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. 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; Kassa, 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 100mg/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 invivo, including cardiorespiratory parameters and temperature, psychomotor development, exploratory behavior, arthro-, nephro- and hepato-toxic effects. We found no effect of Ciprofloxacin at 10 and 30mg/kg/day. In contrast, administration at 100mg/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

  17. 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.

  18. 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

  19. 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.

  20. Fatal Acute Intestinal Pseudoobstruction in Mice

    PubMed Central

    Feinstein, Ricardo E; Morris, Winston E; Waldemarson, Anne Halldn; Hedenqvist, Patricia; Lindberg, Ronny

    2008-01-01

    Here we describe the epizootiology and pathology of spontaneous, fatal acute intestinal pseudoobstruction that occurred in a mouse colony of 1000 breeding pairs, mainly of the C57Bl/6 strain and free from known pathogenic agents. Most of the mice affected were dams in the second week of lactation. At necropsy, segments of the small intestines were distended with fluid contents. Widespread apoptosis of the villus epithelium of the small intestine and superficial epithelial cells of the large intestine, associated with strong expression of active caspase 3, was a distinctive feature. Necrotic enterocytes, mucosal erosions, and acute mucosal inflammation were prominent in some mice, and morphologic signs of toxemia were generally present. No light microscopic neuronal changes were apparent in the gut, and no etiologic agents were identified. These results indicate that sudden activation of apoptosis in the trophically stimulated gut epithelium during peak lactation was instrumental for the fatal outcome of the condition, but the primary cause of the motility dysfunction of the bowel was not established. PMID:18459715

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  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. Photic resetting and entrainment in CLOCK-deficient mice.

    PubMed

    Dallmann, Robert; DeBruyne, Jason P; Weaver, David R

    2011-10-01

    Mice lacking the CLOCK protein have a relatively subtle circadian phenotype, including a slightly shorter period in constant darkness, differences in phase resetting after 4-hour light pulses in the early and late night, and a variably advanced phase angle of entrainment in a light-dark (LD) cycle. The present series of experiments was conducted to more fully characterize the circadian phenotype of Clock(-/-) mice under various lighting conditions. A phase-response curve (PRC) to 4-hour light pulses in free-running mice was conducted; the results confirm that Clock(-/-) mice exhibit very large phase advances after 4-hour light pulses in the late subjective night but have relatively normal responses to light at other phases. The abnormal shape of the PRC to light may explain the tendency of CLOCK-deficient mice to begin activity before lights-out when housed in a 12-hour light:12-hour dark lighting schedule. To assess this relationship further, Clock(-/-) and wild-type control mice were entrained to skeleton lighting cycles (1L:23D and 1L:10D:1L:12D). Comparing entrainment under the 2 types of skeleton photoperiods revealed that exposure to 1-hour light in the morning leads to a phase advance of activity onset (expressed the following afternoon) in Clock(-/-) mice but not in the controls. Constant light typically causes an intensity-dependent increase in circadian period in mice, but this did not occur in CLOCK-deficient mice. The failure of Clock(-/-) mice to respond to the period-lengthening effect of constant light likely results from the increased functional impact of light falling in the phase advance zone of the PRC. Collectively, these experiments reveal that alterations in the response of CLOCK-deficient mice to light in several paradigms are likely due to an imbalance in the shape of the PRC to light. PMID:21921293

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

    PubMed Central

    LU, XIAO-MEI; MA, LING; JIN, YU-NAN; YU, YAN-QIU

    2015-01-01

    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)?, interleukin (IL)-6, IL-4 and IL-10. The protein expression levels of Toll-like receptor (TLR4) and nuclear factor (NF)?B 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, NF?B, TNF?, 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

  10. 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 1? and interferon ? 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-O?-treated HbSS mice infected with S. pneumoniae is associated with altered pulmonary inflammation but not enhanced bacterial clearance. PMID:25429101

  11. 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

  12. 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...

  13. Computerized video analysis of social interactions in mice.

    PubMed

    de Chaumont, Fabrice; Coura, Renata Dos-Santos; Serreau, Pierre; Cressant, Arnaud; Chabout, Jonathan; Granon, Sylvie; Olivo-Marin, Jean-Christophe

    2012-04-01

    The study of social interactions in mice is used as a model for normal and pathological cognitive and emotional processes. But extracting comprehensive behavioral information from videos of interacting mice is still a challenge. We describe a computerized method and software, MiceProfiler, that uses geometrical primitives to model and track two mice without requiring any specific tagging. The program monitors a comprehensive repertoire of behavioral states and their temporal evolution, allowing the identification of key elements that trigger social contact. Using MiceProfiler we studied the role of neuronal nicotinic receptors in the establishment of social interactions and risk-prone postures. We found that the duration and type of social interactions with a conspecific evolves differently over time in mice lacking neuronal nicotinic receptors (Chrnb2-/-, here called ?2(-/-)), compared to C57BL/6J mice, and identified a new type of coordinated posture, called back-to-back posture, that we rarely observed in ?2(-/-) mice. PMID:22388289

  14. The gut microbiota regulates bone mass in mice

    PubMed Central

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

    2012-01-01

    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. 2012 American Society for Bone and Mineral Research. PMID:22407806

  15. Enhanced fear expression in Spir-1 actin organizer mutant mice.

    PubMed

    Pleiser, Sandra; Banchaabouchi, Mumna Al; Samol-Wolf, Annette; Farley, Dominika; Welz, Tobias; Wellbourne-Wood, Joel; Gehring, Isabell; Linkner, Jrn; Faix, Jan; Riemenschneider, Markus J; Dietrich, Susanne; Kerkhoff, Eugen

    2014-01-01

    Spir proteins nucleate actin filaments at vesicle membranes and facilitate intracellular transport processes. The mammalian genome encodes two Spir proteins, namely Spir-1 and Spir-2. While the mouse spir-2 gene has a rather broad expression pattern, high levels of spir-1 expression are restricted to the nervous system, oocytes, and testis. Spir-1 mutant mice generated by a gene trap method have been employed to address Spir-1 function during mouse development and in adult mouse tissues, with a specific emphasis on viability, reproduction, and the nervous system. The gene trap cassette disrupts Spir-1 expression between the N-terminal KIND domain and the WH2 domain cluster. Spir-1 mutant mice are viable and were born in a Mendelian ratio. In accordance with the redundant function of Spir-1 and Spir-2 in oocyte maturation, spir-1 mutant mice are fertile. The overall brain anatomy of spir-1 mutant mice is not altered and visual and motor functions of the mice remain normal. Microscopic analysis shows a slight reduction in the number of dendritic spines on cortical neurons. Detailed behavioral studies of the spir-1 mutant mice, however, unveiled a very specific and highly significant phenotype in terms of fear learning in male mice. In contextual and cued fear conditioning experiments the male spir-1 mutant mice display increased fear memory when compared to their control littermates. Our data point toward a particular function of the vesicle associated Spir-1 actin organizer in neuronal circuits determining fear behavior. PMID:24345451

  16. 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

  17. `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 (p0.05). 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 (p0.05). 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

  18. Pathogenicity test for Listeria monocytogenes using immunocompromised mice.

    PubMed Central

    Stelma, G N; Reyes, A L; Peeler, J T; Francis, D W; Hunt, J M; Spaulding, P L; Johnson, C H; Lovett, J

    1987-01-01

    The lethality of Listeria isolates was determined with normal adult mice and mice that were immunocompromised by treatment with 20 mg of carrageenan per kg. The mean 50% lethal doses (LD50s) of the pathogenic isolates were significantly lower (alpha = 0.05) in the immunocompromised mice than in the untreated mice, with an average reduction of 5.8 log10 units. In contrast, the mean LD50s of the nonpathogenic isolates were lower in the immunocompromised mice by an average of only 0.4 log10 unit, a difference that was not significant (alpha = 0.05). When immunocompromised mice were used, the LD50s of pathogenic Listeria monocytogenes isolates were lower than those of nonpathogenic L. innocua and L. seeligeri isolates by greater than or equal to 6 log10 units and lower than those of nonpathogenic L. ivanovii isolates by greater than or equal to 4 log10 units. Pathogenic L. monocytogenes isolates could be distinguished from nonpathogenic isolates by their ability to cause deaths in immunocompromised mice in 3 days at a dose of approximately 10(4) CFU per mouse. An alternative procedure using iron-overloaded mice failed to effectively differentiate pathogenic Listeria isolates. PMID:3121665

  19. 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

  20. 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.

  1. 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 ...

  2. 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.

  3. 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 ...

  4. 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

  5. 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

  6. 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...

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

    PubMed

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

    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

  8. 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...

  9. 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

  10. Preference for and discrimination of paintings by mice.

    PubMed

    Watanabe, Shigeru

    2013-01-01

    I measured preference for paintings (Renoir vs. Picasso or Kandinsky vs. Mondrian) in mice. In general mice did not display a painting preference except for two mice: one preferred Renoir to Picasso, and the other preferred Kandinsky to Mondrian. Thereafter, I examined discrimination of paintings with new mice. When exposure to paintings of one artist was associated with an injection of morphine (3.0 mg/kg), mice displayed conditioned preference for those paintings, showing discrimination of paintings by Renoir from those by Picasso, and paintings by Kandinsky from those by Mondrian after the conditioning. They also exhibited generalization of the preference to novel paintings of the artists. After conditioning with morphine for a set of paintings consisting of two artists, mice showed discrimination between two sets of paintings also from the two artists but not in association with morphine. These results suggest that mice can discriminate not only between an artist's style but also among paintings of the same artist. When mice were trained to discriminate a pair of paintings by Kandinsky and Renoir in an operant chamber equipped with a touch screen, they showed transfer of the discrimination to new pairs of the artists, but did not show transfer of discrimination of paintings by other artists, suggesting generalization. PMID:23762346

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

    PubMed

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

    2015-07-01

    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

  12. Increased misfolding and truncation of tau in APP/PS1/tau transgenic mice compared to mutant tau mice.

    PubMed

    Hraud, Cline; Goufak, Doris; Ando, Kunie; Leroy, Karelle; Suain, Valrie; Yilmaz, Zehra; De Decker, Robert; Authelet, Michle; Laporte, Vincent; Octave, Jean-Nol; Brion, Jean-Pierre

    2014-02-01

    Neurofibrillary degeneration in transgenic models of tauopathies has been observed to be enhanced when these models are crossed with transgenic models developing an A? pathology. The mechanisms leading to this enhanced tau pathology are not well understood. We have performed a detailed analysis of tau misprocessing in a new transgenic mouse model combining APP, PS1 and tau mutations (5xFADTg30 mice) by comparison with littermates expressing only a FTD mutant tau (Tg30 mice). These 5xFADTg30 mice showed a more severe deficient motor phenotype than Tg30 mice and developed with age a dramatically accelerated NFT load in the brain compared to Tg30 mice. Insoluble tau in 5xFADTg30 mice compared to insoluble tau in Tg30 mice showed increased phosphorylation, enhanced misfolding and truncation changes mimicking more closely the post-translational changes characteristic of PHF-tau in Alzheimer's disease. Endogenous wild-type mouse tau was recruited at much higher levels in insoluble tau in 5xFADTg30 than in Tg30 mice. Extracellular amyloid load, A?40 and A?42, ?-CTFs and ?-CTF phosphorylation levels were lower in 5xFADTg30 mice than in 5xFAD mice. Despite this reduction of A?, a significant hippocampal neuronal loss was observed in 5xFADTg30 but not in 5xFAD mice indicating its closer association with increased tau pathology. This 5xFADTg30 model thus mimics more faithfully tau pathology and neuronal loss observed in AD and suggests that additional post-translational changes in tau and self-recruitment of endogenous tau drive the enhanced tau pathology developing in the presence of A? pathology. PMID:24076100

  13. 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

  14. 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

  15. The peripheral cannabinoid receptor knockout mice: an update

    PubMed Central

    Buckley, N E

    2007-01-01

    This review gives an overview of the CB2 receptor (CB2R) knockout (CB2R?/?) mice phenotype and the work that has been carried out using this mutant mouse. Using the CB2R?/? mice, investigators have discovered the involvement of CB2R on immune cell function and development, infection, embryonic development, bone loss, liver disorders, pain, autoimmune inflammation, allergic dermatitis, atherosclerosis, apoptosis and chemotaxis. Using the CB2R?/? mice, investigators have also found that this receptor is not involved in cannabinoid-induced hypotension. In addition, the CB2R?/? mice have been used to determine specific tissue CB2R expression. The specificity of synthetic cannabinoid agonists, antagonists and anti-CB2R antibodies has been screened using tissues from CB2R?/? mice. Thus, the use of this mouse model has greatly helped reveal the diverse events involving the CB2R, and has aided in drug and antibody screening. PMID:17965741

  16. A quantitative study of cerebrovascular variation in inbred mice.

    PubMed Central

    Ward, R; Collins, R L; Tanguay, G; Miceli, D

    1990-01-01

    The arteries of the base of the mouse brain were examined after perfusion with India ink. A qualitative difference exists between inbred mice of three strains (C57BL/6J, 129/J and BALB/cCF) on the one hand, and genetically defined heterogeneous mice on the other; the latter consistently show anomalies similar to those previously described in genetically undefined rodents, whereas inbred mice do not. A quantitative morphometric analysis of the Circle of Willis of inbred mice was undertaken. The results of this analysis are consistent with the notion that the differences in shape between the circles of Willis of different strains of inbred mice are due to additive genetic variation between these strains. PMID:2074233

  17. Transcutaneous measurement of renal function in conscious mice.

    PubMed

    Schreiber, Andrea; Shulhevich, Yury; Geraci, Stefania; Hesser, Juergen; Stsepankou, Dzmitry; Neudecker, Sabine; Koenig, Stefan; Heinrich, Ralf; Hoecklin, Friederike; Pill, Johannes; Friedemann, Jochen; Schweda, Frank; Gretz, Norbert; Schock-Kusch, Daniel

    2012-09-01

    Determination of glomerular filtration rate (GFR) in conscious mice is cumbersome for the experimenter and stressful for the animals. Here we report on a simple new technique allowing the transcutaneous measurement of GFR in conscious mice. This approach extends our previously developed technique for rats to mice. The technique relies on a miniaturized device equipped with an internal memory that permits the transcutaneous measurement of the elimination kinetics of the fluorescent renal marker FITC-sinistrin. This device is described and validated compared with FITC-sinistrin plasma clearance in healthy, unilaterally nephrectomized and pcy mice. In summary, we describe a technique allowing the measurement of renal function in freely moving mice independent of blood or urine sampling as well as of laboratory assays. PMID:22696603

  18. The genetic basis of adaptive melanism in pocket mice

    PubMed Central

    Nachman, Michael W.; Hoekstra, Hopi E.; D'Agostino, Susan L.

    2003-01-01

    Identifying the genes underlying adaptation is a major challenge in evolutionary biology. Here, we describe the molecular changes underlying adaptive coat color variation in a natural population of rock pocket mice, Chaetodipus intermedius. Rock pocket mice are generally light-colored and live on light-colored rocks. However, populations of dark (melanic) mice are found on dark lava, and this concealing coloration provides protection from avian and mammalian predators. We conducted association studies by using markers in candidate pigmentation genes and discovered four mutations in the melanocortin-1-receptor gene, Mc1r, that seem to be responsible for adaptive melanism in one population of lava-dwelling pocket mice. Interestingly, another melanic population of these mice on a different lava flow shows no association with Mc1r mutations, indicating that adaptive dark color has evolved independently in this species through changes at different genes. PMID:12704245

  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. 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

  1. 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

  2. Gata5 Deficiency Causes Airway Constrictor Hyperresponsiveness in Mice

    PubMed Central

    Chen, Bohao; Moore, Tamson V.; Li, Zhenping; Sperling, Anne I.; Zhang, Chunling; Andrade, Jorge; Rodriguez, Alex; Bahroos, Neil; Huang, Yong; Morrisey, Edward E.; Gruber, Peter J.

    2014-01-01

    Gata5 is a transcription factor expressed in the lung, but its physiological role is unknown. To test whether and how Gata5 regulates airway constrictor responsiveness, we studied Gata5?/?, Gata5+/?, and wild-type mice on the C57BL/6J background. Cholinergic airway constrictor responsiveness was assessed invasively in mice without and with induction of allergic airway inflammation through ovalbumin sensitization and aerosol exposure. Gata5-deficient mice displayed native airway constrictor hyperresponsiveness (AHR) in the absence of allergen-induced inflammation. Gata5-deficient mice retained their relatively greater constrictor responsiveness even in ovalbumin-induced experimental asthma. Gata5 deficiency did not alter the distribution of cell types in bronchoalveolar lavage fluid, but bronchial epithelial mucus metaplasia was more prominent in Gata5?/? mice after allergen challenge. Gene expression profiles revealed that apolipoprotein E (apoE) was the fifth most down-regulated transcript in Gata5-deficient lungs, and quantitative RT-PCR and immunostaining confirmed reduced apoE expression in Gata5?/? mice. Quantitative RT-PCR also revealed increased IL-13 mRNA in the lungs of Gata5-deficient mice. These findings for the first time show that Gata5 regulates apoE and IL-13 expression in vivo and that its deletion causes AHR. Gata5-deficient mice exhibit an airway phenotype that closely resembles that previously reported for apoE?/? mice: both exhibit cholinergic AHR in native and experimental asthma states, and there is excessive goblet cell metaplasia after allergen sensitization and challenge. The Gata5-deficient phenotype also shares features that were previously reported for IL-13treated mice. Together, these results indicate that Gata5 deficiency induces AHR, at least in part, by blunting apoE and increasing IL-13 expression. PMID:24199649

  3. Gata5 deficiency causes airway constrictor hyperresponsiveness in mice.

    PubMed

    Chen, Bohao; Moore, Tamson V; Li, Zhenping; Sperling, Anne I; Zhang, Chunling; Andrade, Jorge; Rodriguez, Alex; Bahroos, Neil; Huang, Yong; Morrisey, Edward E; Gruber, Peter J; Solway, Julian

    2014-04-01

    Gata5 is a transcription factor expressed in the lung, but its physiological role is unknown. To test whether and how Gata5 regulates airway constrictor responsiveness, we studied Gata5(-/-), Gata5(+/-), and wild-type mice on the C57BL/6J background. Cholinergic airway constrictor responsiveness was assessed invasively in mice without and with induction of allergic airway inflammation through ovalbumin sensitization and aerosol exposure. Gata5-deficient mice displayed native airway constrictor hyperresponsiveness (AHR) in the absence of allergen-induced inflammation. Gata5-deficient mice retained their relatively greater constrictor responsiveness even in ovalbumin-induced experimental asthma. Gata5 deficiency did not alter the distribution of cell types in bronchoalveolar lavage fluid, but bronchial epithelial mucus metaplasia was more prominent in Gata5(-/-) mice after allergen challenge. Gene expression profiles revealed that apolipoprotein E (apoE) was the fifth most down-regulated transcript in Gata5-deficient lungs, and quantitative RT-PCR and immunostaining confirmed reduced apoE expression in Gata5(-/-) mice. Quantitative RT-PCR also revealed increased IL-13 mRNA in the lungs of Gata5-deficient mice. These findings for the first time show that Gata5 regulates apoE and IL-13 expression in vivo and that its deletion causes AHR. Gata5-deficient mice exhibit an airway phenotype that closely resembles that previously reported for apoE(-/-) mice: both exhibit cholinergic AHR in native and experimental asthma states, and there is excessive goblet cell metaplasia after allergen sensitization and challenge. The Gata5-deficient phenotype also shares features that were previously reported for IL-13-treated mice. Together, these results indicate that Gata5 deficiency induces AHR, at least in part, by blunting apoE and increasing IL-13 expression. PMID:24199649

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. Antioxidant activity of melatonin in mice.

    PubMed

    Pierrefiche, G; Topall, G; Courboin, G; Henriet, I; Laborit, H

    1993-05-01

    Melatonin (in gum tragacanth as solvent) was administered to mice in the dose range of 100 to 450 mg/kg intraperitoneally. It prevented the increase in plasma glucose resulting from pancreatic toxicity caused by the intravenous administration of alloxan at 40 mg/kg. This action of melatonin was significant and dose-dependent. In parallel work using mouse brain homogenates, melatonin and more so its principal hepatic metabolite, 6-hydroxymelatonin, inhibited the formation of colored products reacting with thiobarbituric acid. Again, this inhibition was significant and dose-dependent. Alloxan-induced diabetes and lipoperoxidation induced by thiobarbituric acid are imputed to the production of oxygen free radicals. The consistent results obtained using these two experimental models show the antioxidant activity of melatonin, both in vivo and in vitro. This effect may be reasonably attributed to the indole structure of the molecule. PMID:8321921

  11. 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

  12. 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.

  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. 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

  15. 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.

  16. 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

  17. Application of Humanized Mice in Immunological Research.

    PubMed

    Tu, Wenwei; Zheng, Jian

    2016-01-01

    During the past decade, the development of humanized mouse models and their general applications in biomedical research greatly accelerated the translation of outcomes obtained from basic research into potential diagnostic and therapeutic strategies in clinic. In this chapter, we firstly present an overview on the history and current progress of diverse humanized mouse models and then focus on those equipped with reconstituted human immune system. The update advancement in the establishment of humanized immune system mice and their applications in the studies of the development of human immune system and the pathogenesis of multiple human immune-related diseases are intensively reviewed here, while the shortcoming and perspective of these potent tools are discussed as well. As a valuable bridge across the gap between bench work and clinical trial, progressive humanized mouse models will undoubtedly continue to play an indispensable role in the wide area of biomedical research. PMID:26530800

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Effect of Prior Exposure to Noninfected Ticks on Susceptibility of Mice to Lyme Disease Spirochetes

    PubMed Central

    Richter, Dania; Spielman, Andrew; Matuschka, Franz-Rainer

    1998-01-01

    To determine whether prior exposure to Nearctic Ixodes vector ticks protects native reservoir mice from tick-borne infection by Lyme disease spirochetes, we compared their infectivities for white-footed mice and laboratory mice that had been repeatedly infested by noninfected deer ticks. Nymphal ticks readily engorged on tick-exposed laboratory mice, but their feeding success on white-footed mice progressively declined. Tick-borne spirochetes readily infected previously tick-infested mice. Thus, prior infestation by Nearctic ticks does not protect sympatric reservoir mice or Palearctic laboratory mice from infection by sympatric tick-borne spirochetes. PMID:9797328

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Increased sensitivity to kindling in mice lacking TSP1.

    PubMed

    Mendus, D; Rankin-Gee, E K; Mustapha, M; Porter, B E

    2015-10-01

    The development of a hyperexcitable neuronal network is thought to be a critical event in epilepsy. Thrombospondins (TSPs) regulate synaptogenesis by binding the neuronal ?2? subunit of the voltage-gated calcium channel. TSPs regulate synapse formation during development and in the mature brain following injury. It is unclear if TSPs are involved in hyperexcitability that contributes to the development of epilepsy. Here we explore the development of epilepsy using a pentylenetetrazole (PTZ) kindling model in mice lacking TSP1 and TSP2. Unexpectedly, we found increased sensitivity to PTZ kindling in mice lacking TSP1, while mice lacking TSP2 kindled similar to wild-type. We found that the increased seizure susceptibility in the TSP1 knockout (KO) mice was not due to a compensatory increase in TSP2 mRNA as TSP1/2 KO mice were sensitive to PTZ, similar to the TSP1 KO mice. Furthermore, there were similar levels of TGF-B signal activation during kindling in the TSP1 KO mice compared to wild-type. We observed decreased expression of voltage-dependent calcium channel subunit CACNA2D1 mRNA in TSP1, TSP2, and TSP1/2 KO mice. Decreased CACNA2D2 mRNA was only detected in mice that lacked TSP1 and ?2?-1/2 protein levels in the cortex were lower in the TSP 1/2 KO mice. CACNA2D2 knockout mice have spontaneous seizures and increased PTZ seizure susceptibility. Here we report similar findings, TSP1, and TSP1/2 KO mice have low levels of CACNA2D2 mRNA expression and ?2?-1/2 receptor level in the cortex, and are more susceptible to seizures. CACNA2D2 mutations in mice and humans can cause epilepsy. Our data suggest TSP1 in particular may control CACNA2D2 levels and could be a modifier of seizure susceptibility. PMID:26241338

  10. 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

  11. Mice do not habituate to metabolism cage housing--a three week study of male BALB/c mice.

    PubMed

    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

  12. 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

  13. 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

  14. AGEMAP: A Gene Expression Database for Aging in Mice

    PubMed Central

    Owen, Art B; Ingram, Donald K; Lustig, Ana; Carter, Arnell; Weeraratna, Ashani T; Taub, Dennis D; Gorospe, Myriam; Mazan-Mamczarz, Krystyna; Lakatta, Edward G; Boheler, Kenneth R; Xu, Xiangru; Mattson, Mark P; Falco, Geppino; Ko, Minoru S. H; Schlessinger, David; Firman, Jeffrey; Kummerfeld, Sarah K; Wood, William H; Zonderman, Alan B; Kim, Stuart K; Becker, Kevin G

    2007-01-01

    We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project) gene expression database, which is a resource that catalogs changes in gene expression as a function of age in mice. The AGEMAP database includes expression changes for 8,932 genes in 16 tissues as a function of age. We found great heterogeneity in the amount of transcriptional changes with age in different tissues. Some tissues displayed large transcriptional differences in old mice, suggesting that these tissues may contribute strongly to organismal decline. Other tissues showed few or no changes in expression with age, indicating strong levels of homeostasis throughout life. Based on the pattern of age-related transcriptional changes, we found that tissues could be classified into one of three aging processes: (1) a pattern common to neural tissues, (2) a pattern for vascular tissues, and (3) a pattern for steroid-responsive tissues. We observed that different tissues age in a coordinated fashion in individual mice, such that certain mice exhibit rapid aging, whereas others exhibit slow aging for multiple tissues. Finally, we compared the transcriptional profiles for aging in mice to those from humans, flies, and worms. We found that genes involved in the electron transport chain show common age regulation in all four species, indicating that these genes may be exceptionally good markers of aging. However, we saw no overall correlation of age regulation between mice and humans, suggesting that aging processes in mice and humans may be fundamentally different. PMID:18081424

  15. Phenotype of cloned mice: development, behavior, and physiology.

    PubMed

    Tamashiro, Kellie L K; Wakayama, Teruhiko; Yamazaki, Yukiko; Akutsu, Hidenori; Woods, Stephen C; Kondo, Sylvia; Yanagimachi, Ryuzo; Sakai, Randall R

    2003-11-01

    Cloning technology has potential to be a valuable tool in basic research, clinical medicine, and agriculture. However, it is critical to determine the consequences of this technique in resulting offspring before widespread use of the technology. Mammalian cloning using somatic cells was first demonstrated in sheep in 1997 and since then has been extended to a number of other species. We examined development, behavior, physiology, and longevity in B6C3F1 female mice cloned from adult cumulus cells. Control mice were naturally fertilized embryos subjected to the same in vitro manipulation and culture conditions as clone embryos. Clones attained developmental milestones similar to controls. Activity level, motor ability and coordination, and learning and memory skills of cloned mice were comparable with controls. Interestingly, clones gained more body weight than controls during adulthood. Increased body weight was attributable to higher body fat and was associated with hyperleptinemia and hyperinsulinemia indicating that cloned mice are obese. Cloned mice were not hyperphagic as adults and had hypersensitive leptin and melanocortin signaling systems. Longevity of cloned mice was comparable with that reported by the National Institute on Aging and the causes of death were typical for this strain of mouse. These studies represent the first comprehensive set of data to characterize cloned mice and provide critical information about the long-term effects of somatic cell cloning. PMID:14610260

  16. Effects of leptin on sympathetic nerve activity in conscious mice

    PubMed Central

    Morgan, Donald A; Despas, Fabien; Rahmouni, Kamal

    2015-01-01

    The adipocyte-derived hormone, leptin, has emerged as an important regulator of regional sympathetic nerve activity (SNA) with pathophysiological implications in obesity. Genetically engineered mice are useful to understand the molecular pathways underlying the SNA responses evoked by leptin. However, so far the effect of leptin on direct SNA in mice has been studied under general anesthesia. Here, we examined the sympathetic responses evoked by leptin in conscious mice. Mice were instrumented, under ketamine/xylazine anesthesia, with renal or lumbar SNA recordings using a thin (40gauge) bipolar platinumiridium wire. The electrodes were exteriorized at the nape of the neck and mice were allowed (5h) to recover from anesthesia. Interestingly, the reflex increases in renal and lumbar SNA caused by sodium nitroprusside (SNP)-induced hypotension was higher in the conscious phase versus the anesthetized state, whereas the increase in both renal and lumbar SNA evoked by leptin did not differ between anesthetized or conscious mice. Next, we assessed whether isoflurane anesthesia would yield a better outcome. Again, the SNP-induced increase in renal SNA and baroreceptor-renal SNA reflex were significantly elevated in the conscious states relative to isoflurane-anesthetized phase, but the renal SNA response induced by leptin in the conscious states were qualitatively comparable to those evoked above. Thus, despite improvement in sympathetic reflexes in conscious mice the sympathetic responses evoked by leptin mimic those induced during anesthesia. PMID:26381017

  17. 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

  18. Effects of leptin on sympathetic nerve activity in conscious mice.

    PubMed

    Morgan, Donald A; Despas, Fabien; Rahmouni, Kamal

    2015-09-01

    The adipocyte-derived hormone, leptin, has emerged as an important regulator of regional sympathetic nerve activity (SNA) with pathophysiological implications in obesity. Genetically engineered mice are useful to understand the molecular pathways underlying the SNA responses evoked by leptin. However, so far the effect of leptin on direct SNA in mice has been studied under general anesthesia. Here, we examined the sympathetic responses evoked by leptin in conscious mice. Mice were instrumented, under ketamine/xylazine anesthesia, with renal or lumbar SNA recordings using a thin (40gauge) bipolar platinum-iridium wire. The electrodes were exteriorized at the nape of the neck and mice were allowed (5h) to recover from anesthesia. Interestingly, the reflex increases in renal and lumbar SNA caused by sodium nitroprusside (SNP)-induced hypotension was higher in the conscious phase versus the anesthetized state, whereas the increase in both renal and lumbar SNA evoked by leptin did not differ between anesthetized or conscious mice. Next, we assessed whether isoflurane anesthesia would yield a better outcome. Again, the SNP-induced increase in renal SNA and baroreceptor-renal SNA reflex were significantly elevated in the conscious states relative to isoflurane-anesthetized phase, but the renal SNA response induced by leptin in the conscious states were qualitatively comparable to those evoked above. Thus, despite improvement in sympathetic reflexes in conscious mice the sympathetic responses evoked by leptin mimic those induced during anesthesia. PMID:26381017

  19. Antibody production and protection against influenza virus in immunodeficient mice.

    PubMed Central

    Lucas, S J; Barry, D W; Kind, P

    1978-01-01

    The roles of T and B cells in the immune response to influenza virus were studied by using mice deficient in either T cells (athymic nude) or immunoglobulin production (CBA/N). The serological responses of these mice to either whole or disrupted A/Aichi/2/68 influenza virus vaccines were examined, and the protective effect of these inoculations was tested by challenge infection with mouse-adapted A/Aichi/2/68 influenza virus. In contrast to normal mice, neither strain of immunodeficient mouse produced detectable serum antibody after inoculation with either type of vaccine. CBA/N mice immunized with intact virus vaccine were protected, however, against subsequent lethal challenge. CBA/N mice inoculated with disrupted virus vaccine and nude mice inoculated with either disrupted or whole virus vaccine were not protected against viral challenge. Evidence of immunological memory was observed in CBA/N and nude mice that had survived live virus challenge after immunization with inactivated vaccine. PMID:307534

  20. 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.

  1. IL-12 Inhibits Lipopolysaccharide Stimulated Osteoclastogenesis in Mice

    PubMed Central

    Yoshimatsu, Masako; Fujimura, Yuji; Kohara, Haruka; Morita, Yukiko; Yoshida, Noriaki

    2015-01-01

    Lipopolysaccharide (LPS) is related to osteoclastogenesis in osteolytic diseases. Interleukin- (IL-) 12 is an inflammatory cytokine that plays a critical role in host defense. In this study, we investigated the effects of IL-12 on LPS-induced osteoclastogenesis. LPS was administered with or without IL-12 into the supracalvariae of mice, and alterations in the calvarial suture were evaluated histochemically. The number of osteoclasts in the calvarial suture and the mRNA level of tartrate-resistant acid phosphatase (TRAP), an osteoclast marker, were lower in mice administered LPS with IL-12 than in mice administered LPS alone. The serum level of tartrate-resistant acid phosphatase 5b (TRACP 5b), a bone resorption marker, was also lower in mice administered LPS with IL-12 than in mice administered LPS alone. These results revealed that IL-12 might inhibit LPS-induced osteoclastogenesis and bone resorption. In TdT-mediated dUTP-biotin nick end-labeling (TUNEL) assays, apoptotic changes in cells were recognized in the calvarial suture in mice administered LPS with IL-12. Furthermore, the mRNA levels of both Fas and FasL were increased in mice administered LPS with IL-12. Taken together, the findings demonstrate that LPS-induced osteoclastogenesis is inhibited by IL-12 and that this might arise through apoptotic changes in osteoclastogenesis-related cells induced by Fas/FasL interactions. PMID:26064997

  2. 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

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

    PubMed

    Gamez-Mendez, Ana Mara; Vargas-Robles, Hilda; Ros, 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

  4. 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 NH?-terminal kinase (JNK) and hypoxia-inducible factor (HIF)-1? 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

  5. VPA-induced apoptosis and behavioral deficits in neonatal mice.

    PubMed

    Yochum, Carrie L; Dowling, Peter; Reuhl, Kenneth R; Wagner, George C; Ming, Xue

    2008-04-01

    Sodium valproate (VPA) administered to neonatal mice causes cognitive and motor deficits similar to those observed in humans with autism. In an effort to further evaluate similarities between early VPA exposure and autism, the present study examined treated mice for deficits in social behavior and neuronal damage. BALB/c mice injected on P14 with 400 mg/kg VPA engaged in fewer social interactions (including ano-genital sniffs, allogrooming, and crawl-under/over behaviors) than control mice. Treated mice also exhibited reduced motor activity in a social context but were not significantly different from controls when motor activity was assessed in non-social settings. A second set of BALB/c mice were treated with VPA on P14 and sacrificed at different times thereafter for histopathological analysis. At time-points 12 and 24 h following VPA, treated mice had up to a 30-fold increase in the number of TUNEL-positive cells in the external granule cell layer of the cerebellum and a 10-fold increase in TUNEL-positive cells in the dentate gyrus of the hippocampus. These observations may provide a histopathological correlate for the social deficits observed following post-natal VPA exposure and supports the use of early VPA administration as an animal model for the study of autism. PMID:18316065

  6. Age-Related Retinopathy in NRF2-Deficient Mice

    PubMed Central

    Wang, Jian; Sternberg, Paul; Freeman, Michael L.; Grossniklaus, Hans E.; Cai, Jiyang

    2011-01-01

    Background Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD-like retinal pathology with aging and to explore the underlying mechanisms. Methods and Findings Eyes of both wild type and Nrf2?/? mice were examined in vivo by fundus photography and electroretinography (ERG). Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf2?/? mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE). Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV) and sub-RPE deposition of inflammatory proteins were present in Nrf2?/? mice after 12 months. Accumulation of autophagy-related vacuoles and multivesicular bodies was identified by electron microcopy both within the RPE and in Bruch's membrane of aged Nrf2?/? mice. Conclusions Our data suggest that disruption of Nfe2l2 gene increased the vulnerability of outer retina to age-related degeneration. NRF2-deficient mice developed ocular pathology similar to cardinal features of human AMD and deregulated autophagy is likely a mechanistic link between oxidative injury and inflammation. The Nrf2?/? mice can provide a novel model for mechanistic and translational research on AMD. PMID:21559389

  7. Modulation of early cellular events in wound healing in mice.

    PubMed

    Kenyon, A J; Michaels, E B

    1983-02-01

    Wound healing experiments were conducted in random-bred Swiss mice to determine the effect on antimicrobial surfactants and macrophage stimulators on wound measurements, histologic repair, and wound breaking strengths. In selection of mice, Sendai virus antibody-positive mice healed more slowly than did mice with no detectable titer to Sendai virus. Studies were conducted with Sendai virus-free mice that had C31G (an antimicrobial surfactant), alkyl amine oxide, zymosan, glucan, or phosphate-buffered isotonic saline solution instilled into full-thickness incised wounds. The early events in the repair process indicated a greater degree of inflammatory response comprised mainly of polymorphonuclear leukocytes with subsequent large numbers of monocytes in C31G and alkyl amine oxide-treated wounds. Although zymosan did not induce as large a number of monocytes, the degree of fibroplasia was as great as in wounds in which numbers were higher. The effect of zymosan could be blocked by the addition of N-alpha-p-tosyl-L-lysine chloromethyl ketone to wounds. Wound breaking strength 3 days after surgery was greatest for glucan-treated mice (134 +/- 37 g) whereas that in C31G-treated mice (77 +/- 31 g) was less than that of the controls (92 +/- 37 g). By day 7, there was no significant difference in breaking strength between control and glucan-treated wounds; however, C31G-treated wounds remained substantially weaker than control wounds. PMID:6299147

  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. Osteoinductive potential of highly purified porous ?-TCP in mice.

    PubMed

    Tsukanaka, Masako; Fujibayashi, Shunsuke; Otsuki, Bungo; Takemoto, Mitsuru; Matsuda, Shuichi

    2015-03-01

    Material-induced osteoinduction of calcium phosphate ceramics has been reported in specific animals. We previously reported that recruitment of tartrate-resistant acid phosphatase (TRAP)-positive cells might be one of the main factors responsible for the difference in the occurrence of material-induced osteoinduction between dogs and rats. In this study, we evaluated the osteoinductive potential of highly purified porous beta-tricalcium phosphate materials (HPP-?-TCP) with two different porosities, 75 and 60 % (Olympus Terumo Biomaterials, Tokyo, Japan), implanted into subcutaneous pockets of FVB and C57BL/6 mice. Twelve weeks after implantation, histological examination and gene expression analysis using reverse transcription-polymerase chain reaction were performed. We observed osteoinduction in half of the HPP-?-TCP materials with 60 % porosity implanted into FVB mice. This group of mice also exhibited the most TRAP-positive cells. Significantly more vessels were found in FVB mice than in C57BL/6 mice, but the greatest number of vessels was counted in implants from materials with 75 % porosity implanted into FVB mice, which did not show osteoinduction. These results indicate that recruitment of TRAP-positive cells is one factor responsible for osteoinduction caused by HPP-?-TCP materials in both FVB mice and dogs. Vessel formation seems to be necessary but appears to be less influential for osteoinduction than TRAP-positive cell recruitment. PMID:25698341

  10. Administration of red ginseng ameliorates memory decline in aged mice

    PubMed Central

    Lee, Yeonju; Oh, Seikwan

    2015-01-01

    Background It has been known that ginseng can be applied as a potential nutraceutical for memory impairment; however, experiments with animals of old age are few. Methods To determine the memory enhancing effect of red ginseng, C57BL/6 mice (21 mo old) were given experimental diet pellets containing 0.12% red ginseng extract (approximately 200 mg/kg/d) for 3 mo. Young and old mice (4 mo and 21 mo old, respectively) were used as the control group. The effect of red ginseng, which ameliorated memory impairment in aged mice, was quantified using Y-maze test, novel objective test, and Morris water maze. Red ginseng ameliorated age-related declines in learning and memory in older mice. In addition, red ginseng's effect on the induction of inducible nitric oxide synthase and proinflammatory cytokines was investigated in the hippocampus of aged mice. Results Red ginseng treatment suppressed the production of age-processed inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-?, and interleukin-1? expressions. Moreover, it was observed that red ginseng had an antioxidative effect on aged mice. The suppressed glutathione level in aged mice was restored with red ginseng treatment. The antioxidative-related enzymes Nrf2 and HO-1 were increased with red ginseng treatment. Conclusion The results revealed that when red ginseng is administered over long periods, age-related decline of learning and memory is ameliorated through anti-inflammatory activity. PMID:26199557

  11. Comparisons between warm and cold water swim stress in mice.

    PubMed

    O'Connor, P; Chipkin, R E

    1984-08-01

    The following experiments evaluated the effects of warm- or cold-water swim stress on tail-flick latencies (TFL) in mice. To first determine the appropriate control group, the TFL's of dry-vs-dunked mice were compared. Dry mice had significantly shorter TFL's than dunked mice, implying that the dampness of the mouse's tail contributed to the increase in the TFL. Therefore, dunked mice were used as the relevant control for the swum mice. Cold water swimming (2 degrees C) produced a significant increase in the TFL; this was not blocked by the opiate antagonist naloxone (3 mg/kg sc) or potentiated by the enkephalinase inhibitor thiorphan (100 mg/kg sc). Warm water swimming (32 degrees C) up to 3 min produced an inconsistent effect on TFL's, implying that the effects were at the threshold of detectability. Naloxone attenuated and thiorphan modestly potentiated the effects of warm water swimming on TFL's. This suggests that warm water swim stress-induced increases in mouse TFL's may involve opioid pathways, whereas cold water swim stress-induced changes in mice TFL's appear not to be opioid mediated. PMID:6589457

  12. Studies of macrophage function during Trichinella spiralis infection in mice.

    PubMed Central

    Wing, E J; Krahenbuhl, J L; Remington, J S

    1979-01-01

    Studies were made to investigate the quantitative and functional changes which occur in peritoneal macrophage populations obtained from mice infected orally with Trichinella spiralis larvae. C57BL/6 mice infected with T. spiralis larvae became parasitized with adult worms which were rejected from the intestine from 14 to 20 days after infection. Infected mice developed a striking increase in peritoneal exudate cells, composed largely of macrophages, which was maximal at from 16 to 18 days after infection. T. spiralis larvae and eosinophils were not seen in the peritoneal exudates. Macrophages from mice infected more than 11 days earlier inhibited DNA synthesis of syngeneic and allogeneic tumour cells, a property atributed to activated macrophages. In addition, macrophages from T. spiralis-infected mice had the functional ability to kill EL-4 tumour cells as measured by 51Cr release. Unlike activated macrophages, however, macrophages from infected mice did not develop the ability to inhibit multiplication of the intracellular pathogen Toxoplasma gondii. These studies demonstrate that T. spiralis infection in mice induces changes in macrophage function that differ from changes associated with infections by intracellular pathogens. PMID:437839

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Serotonin Deficiency Exacerbates Acetaminophen-Induced Liver Toxicity In Mice

    PubMed Central

    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)-1? 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

  20. 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

  1. 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

  2. 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

  3. Procedures for Behavioral Experiments in Head-Fixed Mice

    PubMed Central

    Guo, Zengcai V.; Hires, S. Andrew; Li, Nuo; O'Connor, Daniel H.; Komiyama, Takaki; Ophir, Eran; Huber, Daniel; Bonardi, Claudia; Morandell, Karin; Gutnisky, Diego; Peron, Simon; Xu, Ning-long; Cox, James; Svoboda, Karel

    2014-01-01

    The mouse is an increasingly prominent model for the analysis of mammalian neuronal circuits. Neural circuits ultimately have to be probed during behaviors that engage the circuits. Linking circuit dynamics to behavior requires precise control of sensory stimuli and measurement of body movements. Head-fixation has been used for behavioral research, particularly in non-human primates, to facilitate precise stimulus control, behavioral monitoring and neural recording. However, choice-based, perceptual decision tasks by head-fixed mice have only recently been introduced. Training mice relies on motivating mice using water restriction. Here we describe procedures for head-fixation, water restriction and behavioral training for head-fixed mice, with a focus on active, whisker-based tactile behaviors. In these experiments mice had restricted access to water (typically 1 ml/day). After ten days of water restriction, body weight stabilized at approximately 80% of initial weight. At that point mice were trained to discriminate sensory stimuli using operant conditioning. Head-fixed mice reported stimuli by licking in go/no-go tasks and also using a forced choice paradigm using a dual lickport. In some cases mice learned to discriminate sensory stimuli in a few trials within the first behavioral session. Delay epochs lasting a second or more were used to separate sensation (e.g. tactile exploration) and action (i.e. licking). Mice performed a variety of perceptual decision tasks with high performance for hundreds of trials per behavioral session. Up to four months of continuous water restriction showed no adverse health effects. Behavioral performance correlated with the degree of water restriction, supporting the importance of controlling access to water. These behavioral paradigms can be combined with cellular resolution imaging, random access photostimulation, and whole cell recordings. PMID:24520413

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Feeding-elicited cataplexy in orexin knockout mice

    PubMed Central

    Clark, Erika L.; Baumann, Christian R.; Cano, Georgina; Scammell, Thomas E.; Mochizuki, Takatoshi

    2009-01-01

    Mice lacking orexin/hypocretin signaling have sudden episodes of atonia and paralysis during active wakefulness. These events strongly resemble cataplexy, episodes of sudden muscle weakness triggered by strong positive emotions in people with narcolepsy, but it remains unknown whether murine cataplexy is triggered by positive emotions. To determine whether positive emotions elicit murine cataplexy, we placed orexin knockout (KO) mice on a scheduled feeding protocol with regular or highly palatable food. Baseline sleep/wake behavior was recorded with ad lib regular chow. Mice were then placed on a scheduled feeding protocol in which they received 60% of their normal amount of chow 3 hr after dark onset for the next 10 days. Wild-type and KO mice rapidly entrained to scheduled feeding with regular chow, with more wake and locomotor activity prior to the feeding time. On day 10 of scheduled feeding, orexin KO mice had slightly more cataplexy during the food-anticipation period and more cataplexy in the second half of the dark period, when they may have been foraging for residual food. To test whether more palatable food increases cataplexy, mice were then switched to scheduled feeding with an isocaloric amount of Froot Loops, a food often used as a reward in behavioral studies. With this highly palatable food, orexin KO mice had much more cataplexy during the food-anticipation period and throughout the dark period. The increase in cataplexy with scheduled feeding, especially with highly palatable food, suggests that positive emotions may trigger cataplexy in mice, just as in people with narcolepsy. Establishing this connection helps validate orexin KO mice as an excellent model of human narcolepsy and provides an opportunity to better understand the mechanisms that trigger cataplexy. PMID:19362119

  13. 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

  14. 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.

  15. 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

  16. Skeletal defects in Osterix-Cre transgenic mice.

    PubMed

    Huang, Wei; Olsen, Bjorn R

    2015-02-01

    Cre/loxP recombination is a powerful strategy widely used for in vivo conditional gene targeting. This technique has made possible many important discoveries of gene function in normal and disease biology. However, due to the transgenic nature of most Cre mouse strains undesired phenotypes occasionally occur in Cre mice. Here we report skeletal defects in Osterix-Cre (Osx-Cre) transgenic mice including delayed calvarial ossification and fracture calluses at multiple skeletal sites. These data suggest that Osx-Cre containing controls should be used for both in vivo and in vitro skeletal analyses of conditional knockout mice generated with this Osx-Cre mouse strain. PMID:25139670

  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. 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.

  19. Decreased body weight and hepatic steatosis with altered fatty acid ethanolamide metabolism in aged L-Fabp ?/? mice[S

    PubMed Central

    Newberry, Elizabeth P.; Kennedy, Susan M.; Xie, Yan; Luo, Jianyang; Crooke, Rosanne M.; Graham, Mark J.; Fu, Jin; Piomelli, Daniele; Davidson, Nicholas O.

    2012-01-01

    The tissue-specific sources and regulated production of physiological signals that modulate food intake are incompletely understood. Previous work showed that L-Fabp?/? mice are protected against obesity and hepatic steatosis induced by a high-fat diet, findings at odds with an apparent obesity phenotype in a distinct line of aged L-Fabp?/? mice. Here we show that the lean phenotype in L-Fabp?/? mice is recapitulated in aged, chow-fed mice and correlates with alterations in hepatic, but not intestinal, fatty acid amide metabolism. L-Fabp?/? mice exhibited short-term changes in feeding behavior with decreased food intake, which was associated with reduced abundance of key signaling fatty acid ethanolamides, including oleoylethanolamide (OEA, an agonist of PPAR?) and anandamide (AEA, an agonist of cannabinoid receptors), in the liver. These reductions were associated with increased expression and activity of hepatic fatty acid amide hydrolase-1, the enzyme that degrades both OEA and AEA. Moreover, L-Fabp?/? mice demonstrated attenuated responses to OEA administration, which was completely reversed with an enhanced response after administration of a nonhydrolyzable OEA analog. These findings demonstrate a role for L-Fabp in attenuating obesity and hepatic steatosis, and they suggest that hepatic fatty acid amide metabolism is altered in L-Fabp?/? mice. PMID:22327204

  20. 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

  1. FGF21 mediates alcohol-induced adipose tissue lipolysis by activation of systemic release of catecholamine in mice[S

    PubMed Central

    Zhao, Cuiqing; Liu, Yanlong; Xiao, Jian; Liu, Liming; Chen, Shaoyu; Mohammadi, Moosa; McClain, Craig J.; Li, Xiaokun; Feng, Wenke

    2015-01-01

    Alcohol consumption leads to adipose tissue lipoatrophy and mobilization of FFAs, which contributes to hepatic fat accumulation in alcoholic liver disease. This study aimed to investigate the role of fibroblast growth factor (FGF)21, a metabolic regulator, in the regulation of chronic-binge alcohol-induced adipose tissue lipolysis. FGF21 KO mice were subjected to chronic-binge alcohol exposure, and epididymal white adipose tissue lipolysis and liver steatosis were investigated. Alcohol exposure caused adipose intracellular cAMP elevation and activation of lipolytic enzymes, leading to FFA mobilization in both WT and FGF21 KO mice. However, alcohol-induced systemic elevation of catecholamine, which is known to be a major player in adipose lipolysis by binding to the ?-adrenergic receptor, was markedly inhibited in KO mice. Supplementation with recombinant human FGF21 to alcohol-exposed FGF21 KO mice resulted in an increase in fat loss in parallel with an increase of circulating norepinephrine concentration. Furthermore, alcohol consumption-induced fatty liver was blunted in the KO mice, indicating an inhibition of fatty acid reverse transport from adipose to the liver in the KO mice. Taken together, our studies demonstrate that FGF21 KO mice are protected from alcohol-induced adipose tissue excess-lipolysis through a mechanism involving systemic catecholamine release. PMID:26092866

  2. Chemically and genetically immunocompromised mice are not more susceptible than immunocompetent mice to infection with Cryptosporidium muris.

    PubMed

    Miller, Thomas A; Ware, Michael W; Wymer, Larry J; Schaefer, Frank W

    2007-01-31

    The prevailing paradigm is that immunosuppressed individuals are more susceptible to infection and are at higher risk of infection from Cryptosporidium oocysts if present in drinking water. To test this hypothesis, three immune conditions were examined: genetically immunocompromised T cell deficient CD-1 nude mice, B and T cell deficient Fox Chase CB-17/IcrClB SCID mice, and chemically immunosuppressed C57Bl/6 mice. Chemical immunosuppression was induced with a single subcutaneous injection of methylprednisolone acetate (MPA) at 600 mg/kg. The MPA immunosuppressed C57Bl/6 mice were characterized by a sustained decrease in circulating CD3, CD4 and CD8 T-lymphocytes of greater than 80% and a similar decrease in B-lymphocytes. A sharp rise in circulating mature segmented neutrophils followed MPA injection, dropping sharply after 10-14 days, mirroring the decrease in lymphocytes. The cessation of oocyst production after MPA was not accompanied by a radical rise in circulating CD3 or CD4 T-lymphocytes, but rather a rise in CD8 T-lymphocytes. The ID50 for the MPA immunosuppressed C57Bl/6 mice was 122 oocysts, whereas the ID50 for the C57Bl/6 immunocompetent group was 44. The genetically immunocompromised mice showed similar differences. The ID50 for CD-1 nude mice was 166 oocysts compared to 64 in CD-1 immunocompetent mice. For Fox Chase CB-17/IcrClB SCID and the immunocompetent CB-17 mice, the ID50's were 83 and 60 oocysts, respectively. These results suggest that the lack of an immune response does not increase the ability of C. muris to establish a productive infection and produce oocysts. PMID:16962704

  3. 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

  4. Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

    PubMed

    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 expression-not 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

  5. 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

  6. 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

  7. 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...

  8. 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

  9. 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…

  10. 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

  11. Strain-dependent modulation of memory by stress in mice.

    PubMed

    Castellano, C; Puglisi-Allegra, S

    1983-05-01

    The effects of immobilization stress were investigated in Swiss Webster (Swiss), DBA/2 (DBA), and C57BL/6 (C57) mice, tested in a passive avoidance situation. Retention performance was impaired in Swiss and DBA mice, and improved in C57 mice, immobilized immediately, but not 2 hr, after training. These effects lasted for less than 7 days in DBA and Swiss mice, while they were still present, in the C57 strain, 14 days after training. The naloxone antagonism of the effects observed was also demonstrated. The results are discussed in terms of the possible role of endogenous opioids, stress hormones, and genetic makeup in the stress-induced modulation of memory processes in the mouse. PMID:6626097

  12. BEHAVIORAL TOXICITY OF TRIHALOMETHANE CONTAMINANTS OF DRINKING WATER IN MICE

    EPA Science Inventory

    The behavioral toxicity of trichloromethane (TCM), dichlorobromomethane (DCBM), dibromochloromethane (DBCM) and tribromonethane (TBM) was evaluated following oral administration in mice. A variety of dosage regimens and behavioral measures were used. Studies included acute dose e...

  13. Mice with Mitochondrial Complex I Deficiency Develop a Fatal Encephalomyopathy

    PubMed Central

    Kruse, Shane E.; Watt, William C.; Marcinek, David J.; Kapur, Raj P.; Schenkman, Kenneth A.; Palmiter, Richard D.

    2008-01-01

    SUMMARY To study effects of mitochondria complex I (CI, NADH:ubiquinone oxidoreductase) deficiency, we inactivated the Ndufs4 gene (KO mice), which encodes an 18 kD subunit of the 45-protein complex. Although small, KO mice appeared healthy until ~5 wk of age, when ataxic signs began and progressed until death at ~7 wk. The KO mice manifested encephalomyopathy including a retarded growth rate, lethargy, loss of motor skill, blindness, and elevated serum lactate. CI activity in submitochondrial particles from KO mice was undetectable by spectrophotometric assays. However, CI-driven oxygen consumption by intact tissue was about half that of controls. Native gel electrophoresis revealed reduced levels of intact CI. These data suggest that CI fails to assemble properly or is unstable without Ndufs4. KO muscle has normal morphology but low NADH dehydrogenase activity and subsarcolemmal aggregates of mitochondria. Nonetheless, total oxygen consumption, muscle ATP and phosphocreatine concentrations measured in vivo were within normal parameters. PMID:18396137

  14. 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

  15. 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. ...

  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. ?-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

  18. Muir-Torre-like syndrome in Fhit-deficient mice.

    PubMed

    Fong, L Y; Fidanza, V; Zanesi, N; Lock, L F; Siracusa, L D; Mancini, R; Siprashvili, Z; Ottey, M; Martin, S E; Druck, T; McCue, P A; Croce, C M; Huebner, K

    2000-04-25

    To investigate the role of the Fhit gene in carcinogen induction of neoplasia, we have inactivated one Fhit allele in mouse embryonic stem cells and produced (129/SvJ x C57BL/6J) F(1) mice with a Fhit allele inactivated (+/-). Fhit +/+ and +/- mice were treated intragastrically with nitrosomethylbenzylamine and observed for 10 wk posttreatment. A total of 25% of the +/+ mice developed adenoma or papilloma of the forestomach, whereas 100% of the +/- mice developed multiple tumors that were a mixture of adenomas, squamous papillomas, invasive carcinomas of the forestomach, as well as tumors of sebaceous glands. The visceral and sebaceous tumors, which lacked Fhit protein, were similar to those characteristic of Muir-Torre familial cancer syndrome. PMID:10758156

  19. 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

  20. Administration of Glucosylceramide Ameliorated the Memory Impairment in Aged Mice

    PubMed Central

    Lee, Yeonju; Oliynyk, Sergiy; Jung, Jae-Chul; Han, Jeong Jun; Oh, Seikwan

    2013-01-01

    The function and the role of glucosylceramide have not been well studied in the central nervous system. This study was aimed to investigate the possible roles of glucosylceramide in memory function in aged mice. Glucosylceramide (50?mg/kg, p.o.) showed memory enhancing activity after 3-month treatment in the aged mice (C56BL/6, 1820 months old) through Y-maze, novel objective test, and Morris water maze test. Long-term treatment of glucosylceramide decreased the expression of iNOS and COX-2 in the brain of aged mice. The LPS-induced mRNA level of iNOS, COX-2, IL-1?, and TNF-? was reduced by the acute treatment with glucosylceramide in adult mice. These results suggest that glucosylceramide plays an important role in anti-inflammatory and memory enhancement, and it could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer's disease. PMID:23690856

  1. 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.

  2. Anti-STAT6 CTL activity in Stat6?/? mice

    PubMed Central

    Kaplan, Mark H.; Cundiff, Judy K.; Smith, Jill Stader; Aldrich, Carla J.

    2013-01-01

    The generation of germline gene mutations in mice has been an invaluable tool for experimental biology. However, studying immune responses that develop in the absence of a specific protein that could alter thymic selection complicates experimental interpretations. We observed that CD8+ T cells from Stat6?/? mice displayed autoreactivity to STAT6-expressing cells, associated with specific STAT6 peptides binding to MHC class I molecules. These results suggest caution in interpreting experiments where STAT6-expressing cells are transferred into Stat6?/? mice, or where adoptive transfer of Stat6?/? lymphocytes is performed. Our results further highlight additional considerations when studying immune responses involving cell transfer into gene-deficient mice. PMID:24058815

  3. uPA deficiency exacerbates muscular dystrophy in MDX mice

    PubMed Central

    Suelves, Mnica; Vidal, Berta; Serrano, Antonio L.; Tjwa, Marc; Roma, Josep; Lpez-Alemany, Roser; Luttun, Aernout; de Lagrn, Mara Martnez; Daz, Maria ngels; Jard, Merc; Roig, Manuel; Dierssen, Mara; Dewerchin, Mieke; Carmeliet, Peter; Muoz-Cnoves, Pura

    2007-01-01

    Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (1) by promoting the infiltration of BM-derived inflammatory cells; (2) by preventing the excessive deposition of fibrin; and (3) by promoting myoblast migration. Interestingly, genetic loss of the uPA receptor in mdx mice did not exacerbate muscular dystrophy in mdx mice, suggesting that uPA exerts its effects independently of its receptor. These findings underscore the importance of uPA in muscular dystrophy. PMID:17785520

  4. MuirTorre-like syndrome in Fhit-deficient mice

    PubMed Central

    Fong, Louise Y. Y.; Fidanza, Vincenzo; Zanesi, Nicola; Lock, Leslie F.; Siracusa, Linda D.; Mancini, Rita; Siprashvili, Zurab; Ottey, Michelle; Martin, S. Eric; Druck, Teresa; McCue, Peter A.; Croce, Carlo M.; Huebner, Kay

    2000-01-01

    To investigate the role of the Fhit gene in carcinogen induction of neoplasia, we have inactivated one Fhit allele in mouse embryonic stem cells and produced (129/SvJ C57BL/6J) F1 mice with a Fhit allele inactivated (+/?). Fhit +/+ and +/? mice were treated intragastrically with nitrosomethylbenzylamine and observed for 10 wk posttreatment. A total of 25% of the +/+ mice developed adenoma or papilloma of the forestomach, whereas 100% of the +/? mice developed multiple tumors that were a mixture of adenomas, squamous papillomas, invasive carcinomas of the forestomach, as well as tumors of sebaceous glands. The visceral and sebaceous tumors, which lacked Fhit protein, were similar to those characteristic of MuirTorre familial cancer syndrome. PMID:10758156

  5. 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

  6. Pneumonia in mice inoculated experimentally with Acanthamoeba polyphaga mimivirus.

    PubMed

    Khan, Mohammad; La Scola, Bernard; Lepidi, Hubert; Raoult, Didier

    2007-01-01

    In an attempt to elucidate whether Acanthamoeba polyphaga mimivirus (APM) was pathogenic (i.e., induces histological evidence of inflammation or tissue destruction or both) in mammalian host, we inoculated adult BALB/c (n=6) and C57BL/6 (n=6) mice with APM via intracardiac route. C57BL/6 mice developed histopathological features of pneumonia by post-inoculation day (PID) 3 and BALB/c mice, by PID7. The histopathological features of pneumonia, characterized by the presence of thickened alveolar walls with cellular infiltrates comprising mononuclear leukocytes, macrophages and lymphocytes, diffuse alveolar damages with the formation of hyaline membrane and erythrocytes in the alveolar lumen, were most marked by PID 7. We conclude that APM is pathogenic in mice in experimental conditions. PMID:17188457

  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. Administration of glucosylceramide ameliorated the memory impairment in aged mice.

    PubMed

    Lee, Yeonju; Oliynyk, Sergiy; Jung, Jae-Chul; Han, Jeong Jun; Oh, Seikwan

    2013-01-01

    The function and the role of glucosylceramide have not been well studied in the central nervous system. This study was aimed to investigate the possible roles of glucosylceramide in memory function in aged mice. Glucosylceramide (50?mg/kg, p.o.) showed memory enhancing activity after 3-month treatment in the aged mice (C56BL/6, 18-20 months old) through Y-maze, novel objective test, and Morris water maze test. Long-term treatment of glucosylceramide decreased the expression of iNOS and COX-2 in the brain of aged mice. The LPS-induced mRNA level of iNOS, COX-2, IL-1 ? , and TNF- ? was reduced by the acute treatment with glucosylceramide in adult mice. These results suggest that glucosylceramide plays an important role in anti-inflammatory and memory enhancement, and it could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer's disease. PMID:23690856

  9. 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.

  10. Cloned mice derived from somatic cell nuclei.

    PubMed

    Hosaka, K; Ohi, S; Ando, A; Kobayashi, M; Sato, K

    2000-12-01

    In 1997, a cloned sheep "Dolly" was produced by nuclear transfer of somatic cell. The first birth of cloned mice derived from some somatic cells were succeeded in 1998. At present, it is shown that somatic cells, cumulus cells, fibroblasts and Sertoli cells can be used to the study of cloned animal as nuclear donor. In this study investigation was designed to compare with efficiency on the production of cloned embryos by using the microinjection and the electrofusion methods for nuclear transfer. Oocyte enucleation was performed with a micromanipulator. The oocyte was held by holding pipette, and was enucleated using a beveled pipette. Microinjection method: Cell's nucleus injection was carried out by piezo-micromanipulator. Cytochalasin B treated cumulus cell was aspirated into a injection pipette, and was broken its plasma membrane using the injection pipette. Then, the cumulus cell was injected into the enucleated ooplasm directly. Electrofusion method: The cell was aspirated into a beveled pipette, and then an aspirated cell was inserted into perivitelline space. Then, the pair of enucleated oocyte and cell was fused using electrical cell fusion apparatus. The reconstituted embryos were activated after nuclear transfer using St2+. Reconstituted embryos had been produced by the microinjection showed the embryonic development to over 8-cell stages. But, the rate of fragmentation of reconstituted embryos by the microinjection showed a little high rate in comparison with the electrofusion. When some reconstituted embryos by the microinjection were transplanted to pseudopregnant females' oviduct, 9 fetuses were observed at 14 days post coitum. PMID:11329940

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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 7080%) 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

  16. Rhabdomyosarcomas in aging A/J mice.

    PubMed

    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

  17. 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

  18. Parabiosis in mice: a detailed protocol.

    PubMed

    Kamran, Paniz; Sereti, Konstantina-Ioanna; Zhao, Peng; Ali, Shah R; Weissman, Irving L; Ardehali, Reza

    2013-01-01

    Parabiosis is a surgical union of two organisms allowing sharing of the blood circulation. Attaching the skin of two animals promotes formation of microvasculature at the site of inflammation. Parabiotic partners share their circulating antigens and thus are free of adverse immune reaction. First described by Paul Bert in 1864(1), the parabiosis surgery was refined by Bunster and Meyer in 1933 to improve animal survival(2). In the current protocol, two mice are surgically joined following a modification of the Bunster and Meyer technique. Animals are connected through the elbow and knee joints followed by attachment of the skin allowing firm support that prevents strain on the sutured skin. Herein, we describe in detail the parabiotic joining of a ubiquitous GFP expressing mouse to a wild type (WT) mouse. Two weeks after the procedure, the pair is separated and GFP positive cells can be detected by flow cytometric analysis in the blood circulation of the WT mouse. The blood chimerism allows one to examine the contribution of the circulating cells from one animal in the other. PMID:24145664

  19. 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

  20. 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

  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. Imunocompetent Mice Model for Dengue Virus Infection

    PubMed Central

    Gonalves, Denise; de Queiroz Prado, Rafael; Almeida Xavier, Eric; Cristina de Oliveira, Natlia; da Matta Guedes, Paulo Marcos; da Silva, Joo Santana; Moraes Figueiredo, Luiz Tadeu; Aquino, Victor Hugo

    2012-01-01

    Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV). DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease) in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFN? and TNF? cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines. PMID:22666132

  3. Promotion of lung tumors in mice

    SciTech Connect

    Witschi, H.P.

    1981-01-01

    Several elements of two-stage carcinogenesis apply to the development of lung tumors in mice. At least three agents, identified as promoters, will also enhance tumor formation in lung: phorbol, saccharin, and butylated hydroxytoluene (BHT). The antioxidant BHT is effective only if animals are treated after exposure to an initiating agent. Administration can be delayed up to 5 months after urethan treatment and still enhance tumor formation. BHT enhances lung tumor formation regardless of its route of administration. The lowest dose required to produce an effect has not yet been determined. In at least one mouse strain, BHT also enhances tumor formation in animals initiated with 3-methylcholanthren or diethylnitrosaine. No evidence is available yet to show that BHT would enhance tumor development in animals treated with subcarcinogenic doses of an initiating compound. Nor has it been possible to produce more tumors with BHT in mouse strains which have a low spontaneous tumor incidence and respond poorly to urethan. Neveretheless, the data collected on the effects of BHT on mouse lung tumor development have broadened the concept of two-stage carcinogenesis and complement the evidence for initiation-promotion available for other epithelial tissues. (ERB)

  4. Enhancement of lung tumor formation in mice

    SciTech Connect

    Witschi, H.P.

    1984-01-01

    There is now a great deal of data available to show that butylated hydroxytoluene (BHT) enhances the development of lung tumors in mice. In many ways BHT functions like a promoting agent. Interestingly, it also has tumor enhancing or promoting properties in organs other than mouse lung such as rat liver, rat bladder, possibly rat GI tract and in in vitro systems. The development of lung tumors by BHT may be influenced by comparatively low exposure regimens; the minimum dose found so far to be effective are 6 intraperitoneal injections of 50 mg/kg or a diet containing 500 ppM of BHT for 2 weeks. While these findings seem to require that the continued use of BHT as a food additive needs to be reevaluated it should be mentioned that other considerations have lead to the conclusion that BHT probably has a large margin of safety. This makes it important to establish the mechanism of action of BHT which remains unknown. 41 references, 1 figure, 3 tables.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Experimental sialodacryoadenitis virus infection in severe combined immunodeficient mice.

    PubMed Central

    Percy, D H; Williams, K L; Croy, B A

    1991-01-01

    Mice with a severe combined immunodeficiency in B and T lymphocytes and natural killer cells (SCID-beige) were inoculated intranasally with sialodacryoadenitis (SDA) virus, a coronavirus of rats. Animals were killed at designated intervals and tissues were examined for evidence of viral infection by light microscopy and immunofluorescence microscopy. Based on these criteria, there was no evidence that these immunodeficient mice were susceptible to infection with SDA virus. PMID:1653101

  14. 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

  15. 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

  16. 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

  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 bloodbrain 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. 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

  19. 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

  20. 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.

  1. Multiple Host Barriers Restrict Poliovirus Trafficking in Mice

    PubMed Central

    Pfeiffer, Julie K.

    2008-01-01

    RNA viruses such as poliovirus have high mutation rates, and a diverse viral population is likely required for full virulence. We previously identified limitations on poliovirus spread after peripheral injection of mice expressing the human poliovirus receptor (PVR), and we hypothesized that the host interferon response may contribute to the viral bottlenecks. Here, we examined poliovirus population bottlenecks in PVR mice and in PVR mice that lack the interferon ?/? receptor (PVR-IFNAR?/?), an important component of innate immunity. To monitor population dynamics, we developed a pool of ten marked polioviruses discriminated by a novel hybridization-based assay. Following intramuscular or intraperitoneal injection of the ten-virus pool, a major bottleneck was observed during transit to the brain in PVR mice, but was absent in PVR-IFNAR?/? mice, suggesting that the interferon response was a determinant of the peripheral site-to-brain bottleneck. Since poliovirus infects humans by the fecaloral route, we tested whether bottlenecks exist after oral inoculation of PVR-IFNAR?/? mice. Despite the lack of a bottleneck following peripheral injection of PVR-IFNAR?/? mice, we identified major bottlenecks in orally inoculated animals, suggesting physical barriers may contribute to the oral bottlenecks. Interestingly, two of the three major bottlenecks we identified were partially overcome by pre-treating mice with dextran sulfate sodium, which damages the colonic epithelium. Overall, we found that viral trafficking from the gut to other body sites, including the CNS, is a very dynamic, stochastic process. We propose that multiple host barriers and the resulting limited poliovirus population diversity may help explain the rare occurrence of viral CNS invasion and paralytic poliomyelitis. These natural host barriers are likely to play a role in limiting the spread of many microbes. PMID:18535656

  2. 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

  3. 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

  4. 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

  5. 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

  6. Neuropathological Differences Between Rats and Mice after Spinal Cord Injury

    PubMed Central

    Byrnes, Kimberly R.; Fricke, Stanley T.; Faden, Alan I.

    2010-01-01

    Purpose To investigate the utility of noninvasive magnetic resonance imaging (MRI) protocols to demonstrate pathological differences between rats and mice after SCI. Rats and mice are commonly used to model spinal cord injury (SCI), however histology and immunohistochemistry have shown differences in neuropathology between the two species, including cavity formation and scar/inflammatory responses. Materials and Methods Moderate contusion SCI was performed on adult male rats and mice. At 28 days post-injury, animals underwent T1-weighted (T1W), with or without gadolinium contrast, or T2-weighted (T2W) MRI, to be compared with histology at the same time point. Results In both species, all MRI methods demonstrated changes in spinal cord anatomy. Immunohistochemistry indicated that T2W accurately reflected areas of inflammation and glial scar formation in rats and mice. Quantitation of lesion volume by histology and functional performance correlated best with T2W measurements in both species. Gadolinium contrast accurately reflected the blood-spinal cord-barrier permeability in both species, which appeared greater in rats than in mice. Conclusion These data demonstrate that MRI, with either a T1W or T2W protocol, can effectively distinguish pathological differences between rats and mice. PMID:20882614

  7. Fish oil concentrate delays sensitivity to thermal nociception in mice.

    PubMed

    Veigas, Jyothi M; Williams, Paul J; Halade, Ganesh; Rahman, Mizanur M; Yoneda, Toshiyuki; Fernandes, Gabriel

    2011-05-01

    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

  8. Caloric Restriction Enhances Fear Extinction Learning in Mice

    PubMed Central

    Riddle, Megan C; McKenna, Morgan C; Yoon, Yone J; Pattwell, Siobhan S; Santos, Patricia Mae G; Casey, B J; Glatt, Charles E

    2013-01-01

    Fear extinction learning, the ability to reassess a learned cue of danger as safe when it no longer predicts aversive events, is often dysregulated in anxiety disorders. Selective serotonin reuptake inhibitors (SSRI's) enhance neural plasticity and their ability to enhance fear extinction learning may explain their anxiolytic properties. Caloric restriction (CR) has SSRI-like effects on neural plasticity and anxiety-related behavior. We implemented CR in mice to determine its effects on conditioned-fear responses. Wild type and serotonin transporter (SERT) knockout mice underwent CR for 7 days leading to significant weight loss. Mice were then tested for cued fear learning and anxiety-related behavior. CR markedly enhanced fear extinction learning and its retention in adolescent female mice, and adults of both sexes. These effects of CR were absent in SERT knockout mice. Moreover, CR phenocopied behavioral and molecular effects of chronic fluoxetine, but there was no additive effect of CR in fluoxetine-treated mice. These results demonstrate that CR enhances fear extinction learning through a SERT-dependent mechanism. These results may have implications for eating disorders such as anorexia nervosa (AN), in which there is a high prevalence of anxiety before the onset of dietary restriction and support proposals that in AN, CR is a motivated effort to control dysregulated fear responses and elevated anxiety. PMID:23303073

  9. Fate of erythrocyte Cd-metallothionein in mice

    SciTech Connect

    Tanaka, K.; Min, K.S.; Ohyanagi, N.; Onosaka, S.; Fukuhara, C.

    1986-04-01

    Degradation of metallothionein (MT), which appears in erythrocytes following cadmium (Cd) administration, was investigated in mice. Cd-MT underwent only slight decomposition by hemolysate in an in vitro experiment unlike an 800g supernatant fraction of the liver homogenate. In an in vivo study, (/sup 3/H)diisopropylfluorophosphate was given to mice which had received /sup 109/CdCl2 to investigate the relationship between the decay of /sup 109/Cd-MT in the erythrocyte and the life span of the erythrocyte. A similar reduction pattern of radioactivity of /sup 109/Cd and /sup 3/H was observed. Erythrocytes containing /sup 109/Cd-MT obtained from mice preadministered with /sup 109/CdCl/sub 2/ was transfused to normal mice. The /sup 109/Cd radioactivity of erythrocytes decreased in a manner similar to Cd in erythrocytes of /sup 109/CdCl/sub 2/-administered mice. Contrary to this decrease of erythrocyte Cd in the transfused mice, Cd concentration of the spleen increased markedly. Cd increased also in the liver. These results indicate that erythrocyte MT degrades along with the erythrocyte. The Cd from this MT is deposited in the spleen and liver where blood cells are catabolized.

  10. Decreased albumin mRNA in immunodeficient wasted' mice

    SciTech Connect

    Libertin, C.R.; Buczek, N.; Weaver, P.; Mobarhan, S.; Woloschak, G.E. Argonne National Lab., IL )

    1991-03-15

    Mice bearing the autosomal recessive gene wst (wst/wst) develop a wasting syndrome' that leads to death by 28-32 days of age. These mice have faulty repair of damage induced by ionizing radiation, immunodeficiency at secretory sites, and neurologic abnormalities. In addition to a progressively more apparent wasted phenotype, wst/wst mice show other features of failure to thrive and malnutrition. Daily body weights of the animals revealed a loss in weight between 25 and 30 days of age, a time during which normal littermates were progressively and rapidly gaining weight. Albumin mRNA levels were measured by dilution dot blot hybridizations of liver-derived RNA preparations from wasted mice, littermates, and parental controls. In all wasted mice, albumin mRNA levels were reduced 5 to 10 fold compared to controls. Northern blots revealed that the albumin mRNA present in wasted mice was normal in length though reduced in amount. These results suggest there may be a relationship between low albumin synthesis and the wasting syndrome of the wst/wst mouse.

  11. Hepatocyte tissue factor activates the coagulation cascade in mice.

    PubMed

    Sullivan, Bradley P; Kopec, Anna K; Joshi, Nikita; Cline, Holly; Brown, Juliette A; Bishop, Stephanie C; Kassel, Karen M; Rockwell, Cheryl; Mackman, Nigel; Luyendyk, James P

    2013-03-01

    In this study, we characterized tissue factor (TF) expression in mouse hepatocytes (HPCs) and evaluated its role in mouse models of HPC transplantation and acetaminophen (APAP) overdose. TF expression was significantly reduced in isolated HPCs and liver homogenates from TF(flox/flox)/albumin-Cre mice (HPC(?TF) mice) compared with TF(flox/flox) mice (control mice). Isolated mouse HPCs expressed low levels of TF that clotted factor VII-deficient human plasma. In addition, HPC TF initiated factor Xa generation without exogenous factor VIIa, and TF activity was increased dramatically after cell lysis. Treatment of HPCs with an inhibitory TF antibody or a cell-impermeable lysine-conjugating reagent prior to lysis substantially reduced TF activity, suggesting that TF was mainly present on the cell surface. Thrombin generation was dramatically reduced in APAP-treated HPC(?TF) mice compared with APAP-treated control mice. In addition, thrombin generation was dependent on donor HPC TF expression in a model of HPC transplantation. These results suggest that mouse HPCs constitutively express cell surface TF that mediates activation of coagulation during hepatocellular injury. PMID:23305736

  12. Autobacteriographic studies of clarithromycin and erythromycin in mice

    SciTech Connect

    Kohno, Y.; Ohta, K.; Suwa, T.; Suga, T. )

    1990-04-01

    The antimicrobial activity of clarithromycin was compared with that of erythromycin in experimentally infected mice by whole-body autobacteriography. In mice with systemic staphylococcal infections, the number of vital microbes in the body was relatively low in the early period after oral administration of erythromycin, but increased thereafter to the levels found in nonmedicated control mice. On the other hand, with clarithromycin treatment, a significantly smaller number of microbes was evident throughout the body. The microbes were scarcely seen in the parenchyma of any organs during the examination period. This potent antimicrobial activity of clarithromycin compared with that of erythromycin was further demonstrated in mice with respiratory infections. On the other hand, to examine the distribution properties of both antibiotics in the whole body, an autoradiographic study was carried out with (N-methyl-14C)clarithromycin and (N-methyl-14C)erythromycin. Both labeled antibiotics were distributed widely throughout the body after oral administration in both uninfected control mice and mice with systemic infections. However, the radioactivity was more marked and persistent for (14C)clarithromycin than it was for (14C)erythromycin, particularly in the lungs. The observations described above indicate the superior in vivo antimicrobial activity of clarithromycin compared with that of erythromycin and suggest that the superiority of clarithromycin is largely attributed to its favorable distribution properties. The advantages of whole-body autobacteriography, coupled with whole-body autoradiography, are discussed.

  13. Sudomotor function and sweat gland innervation in galanin knockout mice.

    PubMed

    Vilches, Jorge J; Wynick, David; Kofler, Barbara; Lang, Roland; Navarro, Xavier

    2012-08-01

    The presence of galanin and galanin binding sites in sweat gland has been demonstrated previously. In order to investigate whether galanin can influence sweat gland function, we compared sweating induced in footpads of wild type and galanin knockout mice by cholinergic and thermal stimulation using the silicone impression technique. Pilocarpine injections resulted in a similar number of reactive sweat glands and non-significant difference in the amount of sweat secretion in wild type and galanin knockout mice. However, thermal stimulation led to a significant increase in the number of secreting sweat glands in galanin knockout mice. To further evaluate possible differences in the innervation of sweat glands that could explain differences in their secretory activity, immunohistochemical labeling of cutaneous and sudomotor innervations against protein gene product 9.5, vasoactive intestinal polypeptide and choline acetyltransferase in plantar pads was performed. Immunohistochemical analysis revealed no significant differences in the distribution and intensity of the innervations between wild type mice and galanin knockout mice. Although our results indicate normal cholinergic responses and innervation of the sweat glands in galanin knockout mice, they also demonstrate that galanin plays a role in regulating the sudomotor activity in response to thermal stimulation. PMID:22698811

  14. [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 num