Academic literature on the topic 'C57BL/6 wild-type mice'
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Journal articles on the topic "C57BL/6 wild-type mice"
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Durmus, Nedim, Wen-Chi Chen, Sung-Hyun Park та ін. "Resistin-like Molecule α and Pulmonary Vascular Remodeling: A Multi-Strain Murine Model of Antigen and Urban Ambient Particulate Matter Co-Exposure". International Journal of Molecular Sciences 24, № 15 (2023): 11918. http://dx.doi.org/10.3390/ijms241511918.
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Pulmonary hypertension (PH) has a high mortality and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type-2- and type-17 responses in C57BL/6 mice. Here, we focused on type-2-response-related cytokines, specifically resistin-like molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild-type or RELMα−/− mice. Vascular remodeling was assessed with histology; right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were much more prominent in the C57BL/6 strain. Compared to wild-type mice, RELMα−/− had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV IL-33-receptor were significantly increased in BALB/c wild-type mice, but not in BALB/c-RELMα−/− or in C57BL/6-wild-type or C57BL/6-RELMα−/− mice in response to antigen/PM2.5. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα−/− mice were not different from their respective wild-type controls. The RELMα−/− animals demonstrated significantly decreased expression of RELMβ and RELMγ, which makes these mice comparable to a situation where human RELMβ levels would be significantly modified, as only humans have this single RELM molecule. In BALB/c mice, RELMα was a key contributor to pulmonary vascular remodeling, increase in RV weight and RV cytokine responses induced by exposure to antigen/PM2.5, highlighting the significance of the genetic background for the biological role of RELMα.
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Kenyon, Nicholas J., Albert van der Vliet, Bettina C. Schock, Tatsuya Okamoto, Gabrielle M. McGrew, and Jerold A. Last. "Susceptibility to ozone-induced acute lung injury in iNOS-deficient mice." American Journal of Physiology-Lung Cellular and Molecular Physiology 282, no. 3 (2002): L540—L545. http://dx.doi.org/10.1152/ajplung.00297.2001.
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Mice deficient in inducible nitric oxide synthase (iNOS; C57Bl/6Ai-[KO] NOS2 N5) or wild-type C57Bl/6 mice were exposed to 1 part/million of ozone 8 h/night or to filtered air for three consecutive nights. Endpoints measured included lavagable total protein, macrophage inflammatory protein (MIP)-2, matrix metalloproteinase (MMP)-9, cell content, and tyrosine nitration of whole lung proteins. Ozone exposure caused acute edema and an inflammatory response in the lungs of wild-type mice, as indicated by significant increases in lavage protein content, MIP-2 and MMP-9 content, and polymorphonuclear leukocytes. The iNOS knockout mice showed significantly greater levels of lung injury by all of these criteria than did the wild-type mice. We conclude that iNOS knockout mice are more susceptible to acute lung damage induced by exposure to ozone than are wild-type C57Bl/6 mice and that protein nitration is associated with the degree of inflammation and not dependent on iNOS-derived nitric oxide.
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SINGH, Uma, Shumei ZHONG, Momiao XIONG, Tong-bin LI, Allan SNIDERMAN, and Ba-Bie TENG. "Increased plasma non-esterified fatty acids and platelet-activating factor acetylhydrolase are associated with susceptibility to atherosclerosis in mice." Clinical Science 106, no. 4 (2004): 421–32. http://dx.doi.org/10.1042/cs20030375.
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Animal models provide vital tools to explicate the pathogenesis of atherosclerosis. Accordingly, we established two atherosclerosis-prone mice models: (i) mice lacking the LDL (low-density lipoprotein) receptor (LDLR) and the ability to edit apo (apolipoprotein) B mRNA (Apobec1; designated LDb: LDLR-/-Apobec1-/-), and (ii) mice with the LDb background, who also overexpressed human apoB100 (designated LTp: LDLR-/-Apobec1-/-ERhB+/+). Both LDb and LTp mice had markedly elevated levels of LDL and increased levels of NEFAs (non-esterified fatty acids) compared with C57BL/6 wild-type mice. However, fasting glucose and insulin levels in both animals were not different than those in C57BL/6 wild-type mice. It has been suggested that PAF-AH (platelet-activating factor acetylhydrolase) increases susceptibility to vascular disease. Both LDb and LTp mice had significantly higher PAF-AH mRNA levels compared with C57BL/6 wild-type mice. PAF-AH gene expression was also significantly influenced by age and sex. Interestingly, PAF-AH mRNA levels were significantly higher in both LTp male and female mice than in the LDb mice. This increased PAF-AH gene expression was associated with elevated plasma PAF-AH enzyme activities (LTp>LDb>C57BL/6). Moreover, a greater proportion of PAF-AH activity was associated with the apoB-containing lipoproteins: 29% in LTp and 13% in LDb mice compared with C57BL/6 wild-type animals (6.7%). This may explain why LTp mice developed more atherosclerotic lesions than LDb mice by 8 months of age. In summary, increased plasma NEFAs, PAF-AH mRNA and enzyme activities are associated with accelerated atherogenesis in these animal models.
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Pappo, Jacques, Deirdre Torrey, Lillian Castriotta, Anneli Savinainen, Zita Kabok, and Alexander Ibraghimov. "Helicobacter pylori Infection in Immunized Mice Lacking Major Histocompatibility Complex Class I and Class II Functions." Infection and Immunity 67, no. 1 (1999): 337–41. http://dx.doi.org/10.1128/iai.67.1.337-341.1999.
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ABSTRACT The role of major histocompatibility complex (MHC) class I- and class II-restricted functions in Helicobacter pyloriinfection and immunity upon oral immunization was examined in vivo. Experimental challenge with H. pylori SS1 resulted in significantly greater (P ≤ 0.025) colonization of MHC class I and class II mutant mice than C57BL/6 wild-type mice. Oral immunization with H. pylori whole-cell lysates and cholera toxin adjuvant significantly reduced the magnitude of H. pylori infection in C57BL/6 wild-type (P = 0.0083) and MHC class I knockout mice (P = 0.0048), but it had no effect on the H. pylori infection level in MHC class II-deficient mice. Analysis of the anti-H. pyloriantibody levels in serum showed a dominant serum immunoglobulin G1 (IgG1) response in immunized C57BL/6 wild-type and MHC class I mutant mice but no detectable serum IgG response in MHC class II knockout mice. Populations of T-cell-receptor (TCR) αβ+CD4+ CD54+ cells localized to gastric tissue of immunized C57BL/6 wild-type and MHC class I knockout mice, but TCRαβ+ CD8+ cells predominated in the gastric tissue of immunized MHC class II-deficient mice. These observations show that CD4+ T cells engaged after mucosal immunization may be important for the generation of a protective anti-H. pylori immune response and that CD4+CD8− and CD4− CD8+ T cells regulate the extent of H. pylori infection in vivo.
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Akoum, J., K. Tahiri, F. Etienne, M. T. Corvol, F. Rannou, and C. Nguyen. "AB0063 AGING CARTILAGE IN WILD-TYPE MICE: AN OBSERVATIONAL STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1333.2–1333. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5989.
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Background:Many animal models of osteoarthritis (OA) have been used to study the pathogenesis of cartilage degeneration1. In mice, spontaneous OA can occur in wild-type or genetically modified animals. The first report of spontaneous OA developing in wild-type mice was published in 19562and changes affecting the knee joint were further related to OA by using ultrastructural- histochemical analyses. However, a quantitative assessment of age-related evolution of OA-type cartilage lesions is lacking. The OA Research Society International (OARSI) grading score was adapted to semi-quantify histopathogical changes occurring in OA animal models, including mice3. The OARSI score has been used to describe changes occurring in induced or genetic OA mouse models but not to describe spontaneous age-related evolution of OA-type cartilage lesions in wild-type mice.Objectives:We aimedto describe the spontaneous evolution of age-related changes affecting knee joint articular cartilage, walking speed and a serum biomarker of cartilage remodeling in C57BL/6 wild-type male mice.Methods:Histological changes were assessed by the OARSI score in newborn, 1-week- and 1-, 3-, 6-, 9- and 12-month-old C57BL/6 wild-type male mice, walking speed by the Locotronic system, and serum C-terminal telopeptide of type II collagen (CTX-II) content by ELISA in 1-, 3-, 6-, and 9-month-old C57BL/6 wild-type male mice.Results:Mean (SD) OARSI score increased from 0.2(0.3) to 1.3(0.6) (p=0.03) between 1 and 3 months of age and from 1.3(0.6) to 3.3(0.6) (p=0.04) between 3 and 6 months of age. Mean walking speed was stable between 1 and 6 months of age but decreased from 11.4(1.8) to 3.2(0.8) cm.s-1 (p=0.03) between 6 and 9 months of age. Serum CTX-II content was maximal at 1 month of age, then decreased from 12.2(8.5) to 2.4(8.4) pg/ml (p=0.02) between 1 and 3 months of age, remaining low and stable thereafter.Conclusion:C57BL/6 wild-type male mice showed continuously increasing osteoarthritic changes but delayed decreasing walking speed with age. These variations were maximal between 3 and 9 months of age. Maximal serum CTX-II content preceded these changes.References:[1]McCoy AM. Animal Models of Osteoarthritis: Comparisons and Key Considerations. Vet Pathol. 2015;52(5):803-18.[2]Sokoloff L. Natural history of degenerative joint disease in small laboratory animals.I. Pathological anatomy of degenerative joint disease in mice. AMA Arch Pathol.1956;62(2):118-28.[3]Glasson SS. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis Cartilage. 2010;18 Suppl 3:S17-23.Table 1.Evolution of cartilage changes, walking speed and serum C-terminal telopeptide of type II collagen (CTX-II) concentrations in wild-type C57BL/6 male mice.AgeNew-born1 week1 month3 months6 months9 months12 monthsOARSI score (0 to 6)0.0 (0.0)0.0 (0.0)0.2 (0.3)1.3 (0.6)*3.3 (0.6)*3.7 (0.6)4.3 (0.6)Walking speed (cm.s-1)--10.5 (1.5)11.3 (4.3)11.4 (1.8)3.2 (0.8)*-CTX-II concentrations (pg/ml)--12.2 (8.5)2.4 (8.4)*1.1 (4.0)4.0 (3.8)-N ≥ 3 per timepoint. All results are means (standard deviation). *p<0.05 as compared to the previous timepoint using the non-parametric Mann-Whitney U-test.Figure 1.(A) New born,1-week- and 1-, 3-, 6-, 9- and 12-month-old wild-type C57BL/6 male mice (N=3 per timepoint) knees were evaluated for cartilage changes following OARSI recommended guidelines by 3 independents readers. Each point represents the mean of OARSI score per mice as scored by 3 independent readers.(B) 1-, 3-, 6- and 9-month-old wild-type C57BL/6 male mice were evaluated for walking speed using the Locotronic®system. Each point represents the mean of 3 measures of walking speed per mice. All results are means (SD). *p<0.05 as compared to the previous timepoint using the non-parametric Mann-Whitney U-test.Disclosure of Interests:Joulnar Akoum: None declared, Khadija Tahiri: None declared, François Etienne: None declared, Marie-Thérèse Corvol: None declared, François Rannou Grant/research support from: Pierre Fabre, Fidia, MSD, Pfizer, Bone Therapeutics, Expanscience, Grunenthal, Thuasne, Genévrier, Fondation Arthritis, Consultant of: Pierre Fabre, Fidia, MSD, Pfizer, Bone Therapeutics, Expanscience, Grunenthal, Thuasne, Genévrier, Speakers bureau: Pierre Fabre, Fidia, MSD, Pfizer, Bone Therapeutics, Expanscience, Grunenthal, Thuasne, Christelle Nguyen: None declared
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Zhong, Zifu, João Paulo Portela Catani, Séan Mc Cafferty, et al. "Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine." Vaccines 7, no. 3 (2019): 96. http://dx.doi.org/10.3390/vaccines7030096.
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To combat emerging infectious diseases like Zika virus (ZIKV), synthetic messenger RNAs (mRNAs) encoding viral antigens are very attractive as they allow a rapid, generic, and flexible production of vaccines. In this work, we engineered a self-replicating mRNA (sr-mRNA) vaccine encoding the pre-membrane and envelope (prM-E) glycoproteins of ZIKV. Intradermal electroporation of as few as 1 µg of this mRNA-based ZIKV vaccine induced potent humoral and cellular immune responses in BALB/c and especially IFNAR1-/- C57BL/6 mice, resulting in a complete protection of the latter mice against ZIKV infection. In wild-type C57BL/6 mice, the vaccine resulted in very low seroconversion rates and antibody titers. The potency of the vaccine was inversely related to the dose of mRNA used in wild-type BALB/c or C57BL/6 mice, as robust type I interferon (IFN) response was determined in a reporter mice model (IFN-β+/Δβ-luc). We further investigated the inability of the sr-prM-E-mRNA ZIKV vaccine to raise antibodies in wild-type C57BL/6 mice and found indications that type I IFNs elicited by this naked sr-mRNA vaccine might directly impede the induction of a robust humoral response. Therefore, we assume that the efficacy of sr-mRNA vaccines after intradermal electroporation might be increased by strategies that temper their inherent innate immunogenicity.
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Curran, Shelly, and Joseph Kovacs. "Altered Trained immunity in AID−/− versus wild type mice following infection with Pneumocystis murina." Journal of Immunology 208, no. 1_Supplement (2022): 58.12. http://dx.doi.org/10.4049/jimmunol.208.supp.58.12.
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Abstract Pneumocystis pneumonia continues to be a life-threatening infection in immunocompromised individuals. Dendritic cells are key antigen presenters to CD4+ T cells, which are critical to controlling Pneumocystis infection along with B cells. β-1,3 glucans are found in the cell wall of the cyst form of Pneumocystis. Glucans derived from other fungi have been shown to induce trained immunity. Therefore, we explored if Pneumocystis infection can induce a trained immunity response in C57Bl/6 (wild type) mice following exposure via a natural route of infection. We also tested activation-induced cytidine deaminase knockout mice (AID−/−), a deficiency that affects B cells, in the same infection model to determine whether a mutation known to affect the adaptive immune response can also alter the manifestation of trained immunity. We found that bone marrow derived dendritic cells (BMDCs) from C57BL/6 Pneumocystis exposed mice respond differently to homologous and heterologous antigen stimulation compared to BMDCs from naïve mice. Furthermore, although the differential response between cells from AID−/− exposed and naïve mice exists, specifically the TNFα response is opposite to that from C57BL/6 mice. In addition, when trained immunity was induced in BMDCs derived from naïve C57Bl/6 mice and AID−/− mice, the cytokine response was distinctive between the cells derived from C57BL/6 mice and AID−/− mice. These results suggest that not only can Pneumocystis infection induce trained immunity in BMDCs, this response is alterable by gene mutations traditionally thought to affect the adaptive immune response. Intramural Research Program of the NIH Clinical Center
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Kopić, Alexandra, Karima Benamara, Maria Schuster, et al. "Coagulation phenotype of wild-type mice on different genetic backgrounds." Laboratory Animals 53, no. 1 (2018): 43–52. http://dx.doi.org/10.1177/0023677218811059.
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Genetically engineered mouse models are used to investigate beneficial treatment in haemophilia by comparison with wild-type mice. It has been recognized that wild-type and haemophilic mice of different genetic backgrounds show different bleeding phenotypes. We assessed ex-vivo coagulation parameters in nine wild-type substrains of 129S1/Sv, BALB/c and C57BL/6 mice applying thromboelastography (TEG), activated partial thromboplastin time (aPTT), prothrombin time (PT) and fibrinogen levels. The comprehensive ex-vivo data are discussed in view of results from a tail-tip bleeding assay. Time to first clot formation ( R-time) showed higher within-substrain (CV range: 28–54%) and higher between-substrain (median range: 25.53–42.60 min) variation for BALB/c than for C57BL/6 mice (CV range: 14–31%; median range: 22.45–24.93 min). Median R-time for 129S1/Sv mice was 30.42 min (CV: 33%). No distinct strain differences were observed for maximum amplitude (MA), aPTT, or PT, but males generally showed higher MA and shorter aPTT than females. Males of all substrains had higher fibrinogen levels than females. The heightened in-vivo variability (CV range: 81–171%; median range: 36.00–469.50 mg) in the tail-tip bleeding assay and increased blood loss in wild-type C57BL/6 male mice was not reflected in ex-vivo coagulation parameters. In general, ex-vivo coagulation results appeared consistent within substrains, but showed substrain and sex differences of variable magnitudes. We conclude that alignment of the mouse substrain genetic background to the experimental model is critical to reduce data variability and animal numbers.
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Hertz, Cheryl J., Hanna Filutowicz та John M. Mansfield. "Resistance to the African Trypanosomes Is IFN-γ Dependent". Journal of Immunology 161, № 12 (1998): 6775–83. http://dx.doi.org/10.4049/jimmunol.161.12.6775.
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Abstract The role of variant surface glycoprotein (VSG)-specific Th cell responses in determining resistance to the African trypanosomes was examined by comparing Th cell responses in relatively resistant and susceptible mice as well as in cytokine gene knockout mice infected with Trypanosoma brucei rhodesiense. Resistant B10.BR and C57BL/6 mice expressed Th1 cell cytokine responses to VSG stimulation during infection, while susceptible C3H mice produced weak or no Th1 cell cytokine responses. Neither resistant B10.BR and C57BL/6 mice nor susceptible C3H mice made detectable Th2 cell cytokine responses to parasite Ag. To more closely examine the potential role of IFN-γ and other cytokines in host resistance, we determined the resistance phenotypes and Th cell responses of IFN-γ and IL-4 knockout mice. Infected C57BL/6-IFN-γ knockout mice were as susceptible as C57BL/6-scid mice and made an IL-2, but not an IL-4, cytokine response to VSG, while C57BL/6-IL-4 knockout mice were as resistant as the wild-type strain and exhibited both IL-2 and IFN-γ cytokine responses. Passive transfer of spleen cells from wild-type mice to IFN-γ knockout mice resulted in enhanced survival. Both wild-type and IFN-γ knockout mice controlled parasitemia with VSG-specific Ab responses, although parasitemias were higher in the IFN-γ knockout mice. Overall, this study demonstrates for the first time that relative resistance to African trypanosomes is associated with a strong Th1 cell response to parasite Ags, that IFN-γ, but not IL-4, is linked to host resistance, and that susceptible animals do not make compensatory Th2 cell responses in the absence of Th1 cell cytokine responses.
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Boesteanu, Alina C., Jillian A. Norton, Martin Turner, and Peter D. Katsikis. "The role of p110delta in the immunopathology of influenza virus infection (130.12)." Journal of Immunology 182, no. 1_Supplement (2009): 130.12. http://dx.doi.org/10.4049/jimmunol.182.supp.130.12.
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Abstract Infection of C57Bl/6 mice with influenza virus is accompanied by morbidity manifested as weight loss and lung pathology. We have found that mice that have an inactivating mutation in the leucocyte-specific phosphoinositide kinase 3 (PIK3) isoform p110delta (p110delta-/- on a C57BL/6 background manifest significantly reduced morbidity after influenza virus infection compared to C57BL/6 mice. RAG-/- mice also showed reduced morbidity compared to wild type animals, indicating a role for lymphocytes in this pathology. At day 6 postinfection activated pulmonary T cells and NK cells were greatly reduced in p110delta-/- mice. At day 10 postinfection, however, numbers of lymphocytes, B cells, CD4+ T cells, macrophages and granulocytes infiltrating the lungs of p110delta-/- mice were reduced compared to C57Bl/6 mice, without reaching statistical significance. Total number of CD8+ and virus-specific CD8+ T cells found in the lungs of infected p110delta-/- mice were significantly reduced by 2-fold compared to wild-type mice (p=0.03 for both). However, this reduction in the magnitude of the immune response did not affect viral clearance. Our data suggest that p110delta plays an important role in the lymphocyte mediated immunopathology associated with influenza virus infection and suggests that p110delta may be an important therapeutic target for influenza virus infection.
Dissertations / Theses on the topic "C57BL/6 wild-type mice"
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Vulin, Johann. "Caractérisation des agents infectieux responsables de deux maladies à prion : l'ESB atypique de type H chez les bovins et la tremblante de type "CH1641" chez les petits ruminants." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10210.
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Nous avons entrepris la caractérisation de la protéine prion pathologique par Western blot à partir d’isolats de petits ruminants et de bovins atteints d’Encéphalopathie Spongiforme Subaiguë Transmissible (ESST) afin d’identifier des signatures moléculaires divergeant de la signature associée à l’ESST affectant habituellement ces animaux ; la tremblante classique pour les petits ruminants et l’ESB classique (ESB-C) pour les bovins. Cette étude a permis d’évaluer la fréquence de phénotypes inhabituels et a contribué à envisager les formes d’ESB atypiques comme sporadiques. Ensuite la transmission des isolats de petits ruminants aux souris C57Bl/6 et TgOvPrP4 a permis d’une part de confirmer l’absence de contamination par l’agent de l’ESB, tout du moins pour les ovins, et d’autre part d’approfondir les connaissances sur la diversité des souches dans les isolats de tremblante. Les travaux de transmission aux souris C57Bl/6 des isolats bovins atteints d’ESB-H ont quant à eux conduit à la description de l’émergence d’une souche présentant les caractéristiques de l’ESB-C suggérant que la forme sporadique d’ESB-H puisse être à l’origine de la contamination initiale des bovins ayant conduit après recyclage par le biais des farines de viande et d’os à l’épizootie d’ESB-C<br>Molecular characterization using Western blot method has been carried out to identify unusual PrPres pattern from small ruminants and bovines TSE affected. Such analyse allow us to define the frequency of these unusual signature and contribute to consider BSE-H as sporadic form of ruminant TSE. Transmission studies from unusual sheep isolates in C57Bl/6 and TgovPrP4 mice firstly contribute to confirm that none of these sheep isolates was infected by BSE transmission. Secondly, strain characteristics observed through experimental transmission of unusual isolates and classical scrapie affected isolates show results that give some element about strain diversity in both scrapie types. Serial passages of H-BSE in C57Bl/6 mice show the emergence of a prion strain with features similar to classical BSE. Such findings might help to explain the origin of the classical BSE epizootic disease, which could have originated from this kind of sporadic form of BSE
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BERNARDO, Ana Karolina de Santana Nunes. "Avaliação dos efeitos do inibidor de fosfodiesterase-5 sobre os mecanismos regulatórios da neuroinflamação, em modelo de desmielinização induzido em camundongos C57BL/6 wild type e knockout para iNOS." Universidade Federal de Pernambuco, 2016. https://repositorio.ufpe.br/handle/123456789/17352.
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Previous issue date: 2016-02-19<br>O Sildenafil (Viagra®) é um inibidor potente e seletivo da fosfodiesterase-5 (PDE5), enzima
responsável pela hidrólise do monofosfato de guanosina cíclico (GMPc). Tem sido
demonstrado que Sildenafil tem potencial eficácia em desordens patológicas de carater
neuroinflamatório e neurodegenrativo no sistema nervoso central (SNC). A inflamação
cerebral é mediada/modulada por citocinas pró-inflamatórias e pelo NO e exerce um papel
central em numerosas patologias do cérebro, incluindo a esclerose múltipla (EM). A EM é
uma doença inflamatória crônica, com início típico durante os anos produtivos (entre 20 e 50
anos), caracterizada por desmielinização das células nervosas, que leva à severa deficiência
psicomotora. Recentemente foi demonstrado que a administração de Sildenafil promoveu a
inativação das células microgliais e astrocitária, reduziu os fenômenos inflamatórios e danos
causados à mielina em modelo de EM. No entanto, o mecanismo de ação desse fármaco
ainda é desconhecido. Desta forma, o presente estudo investigou os efeitos do Sildenafil sobre
os mecanismos regulatórios do processso na neuroinflamação em modelo de desmielinização
induzido por Cuprizona. Os resultados demonstraram que Sildenafil 25 mg/kg reduziu a
expressão das citocinas inflamatórias IL-1β e TNF-α e aumentou a expressão da citocina antiinflamatória
IL-10. Em adição, o tratamento com Sildenafil reduziu a expressão de de GFAP
(gliose), NFκB (fator de transcrição nuclear para citocinas), AMPK inativo (proteina
reguladora de metabolismo) e iNOS (sintase de óxido nítrico induzível) e aumentou o IKBα
(proteína inibitória NFκB). Os efeitos do sildenafil sobre a remielinização foi observado
através de imagens por ressonância magnética, que demonstrou recuperação de tecido
neuronal degenerado (corpo caloso). Além disso, o tratamento aumentou a expressão de
MMP-9,MCP-1/CCR-2, contribuindo possivelmente para a troca de fenótipo microglial, que
favorece a limpeza de debris mielínicos. Em paralelo, a integridade da mielina foi
demonstrada através do aumento da marcação para oligodendrócitos maduros (GST-pi),
proteína básica da mielina (MBP) e organização de lamelas mielínicas. Em camundongos
knockout iNOS-/-, Sildenafil reduziu os níveis de IL-1β, Iba-1, IFN-γ e não alterou a
expressão de GFAP, TNF-α e COX-2. Sildenafil elevou os níveis GST-pi e melhorou a
estrutura da mielina.Os efeitos do Sildenafil sobre as células astrocitárias demonstrou que o
tratamento preventivo e terapêutico foram eficiente em reduzir a gliose astrocitária induzido
por LPS. Além disso, os tratamentos com sildenafil promoveu diminuição das ondas de cálcio
e do estresse fibras de actina. Diante disso, o presente estudo propõe que o mecanismo de
ação envolve a via AMPK–eNOS-IKβα–NFκB, bem como ação de MMP-9 e MCP-1/ CCR-2
no processo de remielinização. O presente estudo abre novas possibilidades de investigação
para o tratamento de doenças neurodegenerativas, tais como a esclerose múltipla<br>Sildenafil (Viagra) is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), the
enzyme responsible for the hydrolysis of cyclic guanosine monophosphate (cGMP). It has
been shown that sildenafil has potential efficacy in pathological disorders and
neuroinflammatory character neurodegenrativo the central nervous system (CNS). Cerebral
inflammation is mediated / modulated by pro-inflammatory cytokines and NO by and plays a
central role in numerous pathologies of the brain including multiple sclerosis (MS). MS is a
chronic inflammatory disease with typical onset during the productive years (20 to 50),
characterized by demyelination of the nerve cells, which leads to severe psychomotor
impairment. It has recently been shown that sildenafil promoted inactivation of microglial
cells and astrocytes, reduced inflammatory phenomena and damage to myelin in MS model.
However, the mechanism of action of this drug is still unknown. Thus, the present study
investigated the effects of Sildenafil on the regulatory mechanisms in the processso in
neuroinflammation model of demyelination induced cuprizone. The results showed that
Sildenafil 25 mg / kg reduced the expression of inflammatory cytokines IL-1β and TNF-α
expression and increased anti-inflammatory cytokine IL-10. In addition, treatment with
sildenafil reduced expression of GFAP (glial), NFκB (nuclear transcription factor cytokines),
inactive AMPK (regulating protein metabolism) and iNOS (nitric oxide synthase) and
increased IKBα (protein NFκB inhibitory). The effects of sildenafil on remyelination was
observed by magnetic resonance imaging, which showed recovery of degenerated neuronal
tissue (corpus callosum). Furthermore, the treatment increased the expression of MMP-9,
MCP-1 / CCR-2, possibly contributing to the exchange of microglial phenotype, which favors
the cleaning of myelin debris. In parallel, the integrity of the myelin has been demonstrated by
increasing the marking to mature oligodendrocytes (GST-pi), myelin basic protein (MBP) and
myelin lamellae organization. In knockout mice iNOS - / - Sildenafil reduced IL-1β levels,
Iba-1, IFN-γ and did not alter the expression of GFAP, TNF-α and COX-2. Sildenafil raised
the GST-pi levels and improved the structure of mielina.Os effects of sildenafil on astrocytic
cells demonstrated that the preventive and therapeutic treatment were effective in reducing
astrocytic gliosis induced by LPS. In addition, treatment with sildenafil promoted reduction of
calcium waves and actin stress fibers. Thus, the present study suggests that the mechanism of
action involves the AMPK-eNOS-IKβα-NFκB and MMP-9 activity and MCP-1 / CCR-2 in
the remyelination process. This study opens new possibilities for research into the treatment
of neurodegenerative diseases such as multiple sclerosis
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NUNES, Ana Karolina de Santana. "Avaliação dos efeitos do inibidor de fosfodiesterase-5 sobre as células gliais e a re-mielinização, em modelo de desmielinização induzido em camudongos C57BL/6 WILD TYPE e KONCKOUT para iNOS." Universidade Federal de Pernambuco, 2012. https://repositorio.ufpe.br/handle/123456789/12599.
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Previous issue date: 2012-02-10<br>CNPQ; FACEPE<br>O Sildenafil (Viagra®) promove acúmulo de monofosfato de guanosina cíclico (GMPc) através da inibição seletiva da fosfodiesterase-5 (PDE5). Embora esse medicamento mantenha um excelente nível de segurança e perfil de tolerabilidade, apenas disfunção erétil e, mais recentemente, hipertensão pulmonar são doenças tratadas atualmente com Sildenafil. Astrócitos e micróglia são células do SNC que exercem um papel importante em numerosas patologias do cérebro, incluindo a Esclerose Múltipla (EM). A EM é uma doença inflamatória crônica, caracterizada por desmielinização das células nervosas, que leva a severa deficiência psicomotora. Tem sido reportado que o acúmulo intracelular de GMPc modula a reação microglial e astrocitária e protege oligodendrócitos diferenciados (formadores da mielina), reduzindo danos causados à mielinização. Portanto, o presente estudo investigou os efeitos do Sildenafil em modelo de EM induzido pela ingesta de Cuprizona. Cinco camundongos C57BL/6 selvagens e cinco iNOS-/-, machos, com 7-10 semanas de idade, foram usados por grupo. Os grupos receberam, durante quatro semanas: 1) Cuprizona 0,2% misturada na ração, 2) Cuprizona na ração e Sildenafil 3, 25 ou 50 mg/Kg na água de beber (os iNOS-/- receberam apenas a dose de 25 mg/Kg), ou 3) Os controles receberam água e ração puras. Após os tratamentos, os cerebelos foram processados de acordo com a rotina para microscopia eletrônica de transmissão, western blotting, imunohistoquímica (parafina), imunofluorescência (congelação) ou coloração Luxol Fast Blue. Os resultados demonstraram que, nos animais selvagens, Cuprizona induziu temores, limitações motoras e alterações posturais nos animais, aumentou os níveis das proteínas GFAP e Iba-1, indicando gliose reativa e ativação microglial e aumentou COX-2, indicando um ambiente pró-inflamatório no cerebelo; além disso, provocou redução da espessura da mielina e da intensidade de mielinização e promoveu alterações ultraestruturais na bainha de mielina e nos axônios do cerebelo. Sildenafil protegeu significativamente o microambiente neural dos animais tratados com Cuprizona, apresentando efeito dose-dependente, cuja dose mais efetiva foi a de 25 mg/Kg. O tratamento com Sildenafil diminuiu os tremores e limitações motoras induzidos pela Cuprizona, manteve a expressão basal de GFAP e Iba-1, diminuiu fortemente a expressão de COX-2 e das citocinas pró-inflamatórias (IFN-γ, TNF-α, , IL-1β e IL-2), impediu a desmielinização e protegeu ultraestruturalmente a organização mielínica e axonal. Nos animais iNOS-/-, os efeitos clínicos induzidos pela Cuprizona foram semelhantes aos vistos nos animais selvagens e Sildenafil diminuiu esses efeitos. Cuprizona aumentou a expressão de GFAP, Iba-1 e IFN-γ. Nesses animais, entretanto, Sildenafil aumentou a marcação para GFAP, indicando que não teve efeito protetor nos astrócitos, na ausência do NO produzido pela iNOS. Por outro lado, diminuiu a expressão de Iba-1 e IFN-γ, indicando efeito anti-inflamatório e inativação da micróglia estimulada pela Cuprizona. Os animais iNOS-/- controle (sem nenhum tratamento) apresentaram alterações degenerativas na mielina, que foram agravadas pela Cuprizona. Sildenafil diminuiu a intensidade dessas alterações, embora não tenha resolvido-as completamente. Portanto, o aumento dos níveis de GMPc, pela inibição da PDE5, provavelmente agiu como antiinflamatório e agente protetor de astrócitos, micróglia e oligodendrócitos, diminuindo os danos ao tecido neural. Interessantemente, a via de ação do Sildenafil foi tipo celular-dependente, ou seja, foi independente do NO produzido pela iNOS em micróglia e oligodendrócitos e dependente em astrócitos. Portanto, após ensaios clínicos, o Sildenafil pode ser um medicamento compatível com a administração oral para a população com EM e outras doenças neurodegenerativas, promovendo efeitos benéficos adicionais aos tratamentos atuais. Esclarecer o mecanismo de ação do Sildenafil nas células neurais será alvo de estudos futuros do nosso grupo.
Books on the topic "C57BL/6 wild-type mice"
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Hesse, Lautaro Daniel. Estudio del impacto de la ausencia de Kir6.2/K-ATP en la regeneración hepática posterior a una hepatectomía parcial. Teseo, 2022. http://dx.doi.org/10.55778/ts878848969.
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<p>Comprender los mecanismos que rigen la regeneración hepática es crucial para el manejo apropiado de los procesos regenerativos y el desarrollo de nuevas terapias en situaciones donde es necesario recuperar la masa hepática perdida. Se plantea la siguiente pregunta: ¿Existe alguna relación entre la expresión de Kir6.2 y la regeneración hepática posterior a una hepatectomía parcial (HP)? Se utilizaron ratones de las cepas C57BL/6 (WT, <i>wild-type</i>) como animales control, y ratones <i>knockout</i> para Kir6.2 (Kir-/-), los cuales fueron sometidos a HP de dos tercios. La regeneración hepática posterior a la hepatectomía se evaluó a diferentes tiempos que representan las distintas fases de la regeneración. Se determinó el índice peso hígado/peso corporal (PH/PC). Se determinó el perfil de las transaminasas séricas. Se detectó el antígeno nuclear de proliferación celular (PCNA) y ciclina D1. Se estableció el índice apoptótico mediante la determinación entre la proteína Bax y las proteínas antiapoptóticas Bcl-2/Bcl-xL. En conclusión, la ausencia de la proteína Kir6.2 tiene un impacto negativo en la proliferación que se produce luego de la resección de una parte de la masa hepática. En los ratones carentes de Kir6.2 la regeneración también puede verse comprometida por una mayor tasa de apoptosis. El presente estudio proporciona, por primera vez, evidencias claras de que la proteína Kir6.2 participa en el fenómeno regenerativo luego de una HP de dos tercios en ratones.</p>
Book chapters on the topic "C57BL/6 wild-type mice"
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Pyo, Hyun Mi, Jie Yun Park, Sue Nie Park, Hyun Su Kim, Kee Sun Shin, and Har Young Poo. "Immunization with Virus-Like Particle of Human Papillomavirus Type 16 L1 Elicits CTL Immune Response in C57BL/6 Mice." In Key Engineering Materials. Trans Tech Publications Ltd., 2005. http://dx.doi.org/10.4028/0-87849-958-x.119.
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Jana, Rishika, Souvik Karmakar, Bishal Hazra, Subhadeep Roy, and Jayasri Das Sarma. "Mice as an Experimental Model to Understand the Pathobiology of Diseases." In Rodents and Their Role in Ecology, Medicine and Agriculture [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.1001835.
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Murine models are widely used in scientific research because they share many genetic similarities with humans, making them a valuable tool for studying various diseases. C57BL/6 is an experimental mouse model to study the demyelination and inflammation etiology of Multiple Sclerosis (MS). Intracranial inoculation of neurotropic murine β-coronavirus strain of Mouse hepatitis virus in C57BL/6 mice induces demyelination with or without axonal loss, providing many insights regarding the mechanism of MS as well as SARS-CoV-2 mediated pulmonary and neuro pathology in humans. By selectively using knockout mice in the wild-type C57BL/6 background, researchers can gain insights into the immunomodulatory nexus and can identify pathways involved in immune regulation which further can be efficiently studied with CD4-/-, CD40-/- and CD40L-/- mice. In addition, C57BL/6 mice can also be used to generate syngeneic mouse models to investigate the etiology and mechanism of various cancers, including ovarian cancer. Similarly, along with C57BL/6 mice, different immunocompromised mice models, such as nude mice, SCID mice, and NOD/SCID mice, can be used to study the etiology, host-tumour interaction, function of the microenvironment, and tumour heterogeneity in tumour metastasis.
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Kaur, Harpreet, Svetlana Golovko, Mikhail Y. Golovko, Surjeet Singh, Diane C. Darland, and Colin K. Combs. "Effects of Probiotic Supplementation on Short Chain Fatty Acids in the AppNL–G–F Mouse Model of Alzheimer’s Disease." In Advances in Alzheimer’s Disease. IOS Press, 2022. http://dx.doi.org/10.3233/aiad220028.
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Background: The intestinal microbiota and its metabolites, particularly short-chain fatty acids (SCFAs), have been implicated in immune function, host metabolism, and even behavior. Objective: This study was performed to investigate whether probiotic administration influences levels of intestinal microbiota and their metabolites in a fashion that may attenuate brain changes in a mouse model of Alzheimer’s disease (AD). Methods: C57BL/6 wild-type (WT) mice were compared to AppNL–G–F mice. The animals were treated with either vehicle or probiotic (VSL#3) for 8 weeks. Fecal microbiome analysis along with Aβ, GFAP, Iba-1, c-Fos, and Ki-67 immunohisto-chemistry was done. SCFAs were analyzed in serum and brains using UPLC-MS/MS. Results: Probiotic (VSL#3) supplementation for 2 months resulted in altered microbiota in both WT and AppNL–G–F mice. An increase in serum SCFAs acetate, butyrate, and lactate were found in both genotypes following VSL#3 treatment. Propionate and isobutyrate were only increased in AppNL–G–F mice. Surprisingly, VSL#3 only increased lactate and acetate in brains of AppNL–G–F mice. No significant differences were observed between vehicle and VSL#3 fed AppNL–G–F hippocampal immunoreactivities of Aβ, GFAP, Iba-1, and Ki-67. However, hippocampal c-Fos staining increased in VSL#3 fed AppNL–G–F mice. Conclusion: These data demonstrate intestinal dysbiosis in the AppNL–G–F mouse model of AD. Probiotic VSL#3 feeding altered both serum and brain levels of lactate and acetate in AppNL–G–F mice correlating with increased expression of the neuronal activity marker, c-Fos.
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Sahu, Bijayani, Amy R. Mackos, Angela M. Floden, Loren E. Wold, and Colin K. Combs. "Particulate Matter Exposure Exacerbates Amyloid-β Plaque Deposition and Gliosis in APP/PS1 Mice." In Advances in Alzheimer’s Disease. IOS Press, 2021. http://dx.doi.org/10.3233/aiad210013.
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Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and neuronal death. There are several well-established genetic and environmental factors hypothesized to contribute to AD progression including air pollution. However, the molecular mechanisms by which air pollution exacerbates AD are unclear. Objective: This study explored the effects of particulate matter exposure on AD-related brain changes using the APP/PS1 transgenic model of disease. Methods: Male C57BL/6;C3H wild type and APP/PS1 mice were exposed to either filtered air (FA) or particulate matter sized under 2.5 μm (PM2.5) for 6 h/day, 5 days/week for 3 months and brains were collected. Immunohistochemistry for Aβ, GFAP, Iba1, and CD68 and western blot analysis for PS1, BACE, APP, GFAP, and Iba1 were performed. Aβ ELISAs and cytokine arrays were performed on frozen hippocampal and cortical lysates, respectively. Results: The Aβ plaque load was significantly increased in the hippocampus of PM2.5-exposed APP/PS1 mice compared to their respective FA controls. Additionally, in the PM2.5-exposed APP/PS1 group, increased astrocytosis and microgliosis were observed as indicated by elevated GFAP, Iba1, and CD68 immunoreactivities. PM2.5 exposure also led to an elevation in the levels of PS1 and BACE in APP/PS1 mice. The cytokines TNF-α, IL-6, IL-1β, IFN-γ, and MIP-3α were also elevated in the cortices of PM2.5-exposed APP/PS1 mice compared to FA controls. Conclusion: Our data suggest that chronic particulate matter exposure exacerbates AD by increasing Aβ plaque load, gliosis, and the brain inflammatory status.
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Armstrong, Tyler D., Usa Suwannasual, Conner L. Kennedy, et al. "Exposure to Traffic-Generated Pollutants Exacerbates the Expression of Factors Associated with the Pathophysiology of Alzheimer’s Disease in Aged C57BL/6 Wild-Type Mice." In Advances in Alzheimer’s Disease. IOS Press, 2021. http://dx.doi.org/10.3233/aiad210017.
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Background: Multiple studies report a strong correlation between traffic-generated air pollution-exposure and detrimental outcomes in the central nervous system (CNS), including Alzheimer’s disease (AD). Incidence of AD is rapidly increasing and, worldwide, many live in regions where pollutants exceed regulatory standards. Thus, it is imperative to identify environmental pollutants that contribute to AD, and the mechanisms involved. Objective: We investigated the effects of mixed gasoline and diesel engine emissions (MVE) on the expression of factors involved in progression of AD in the hippocampus and cerebrum in a young versus aged mouse model. Methods: Young (2 months old) and aged (18 months old) male C57BL/6 mice were exposed to either MVE (300 μg/m3 PM) or filtered air (FA) for 6 h/d, 7 d/wk, for 50 d. Immunofluorescence and RT-qPCR were used to quantify oxidative stress (8-OHdG) and expression of amyloid-β protein precursor (AβPP), β secretase (BACE1), amyloid-β (Aβ), aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP) 1B1, angiotensin-converting enzyme (ACE1), and angiotensin II type 1 (AT1) receptor in the cerebrum and hippocampus, in addition to cerebral microvascular tight junction (TJ) protein expression. Results: We observed age-related increases in oxidative stress, AhR, CYP1B1, Aβ, BACE1, and AT1 receptor in the CA1 region of the hippocampus, and elevation of cerebral AβPP, AhR, and CYP1B1 mRNA, associated with decreased cerebral microvascular TJ protein claudin-5. MVE-exposure resulted in further promotion of oxidative stress, and significant increases in AhR, CYP1B1, BACE1, ACE1, and Aβ, compared to the young and aged FA-exposed mice. Conclusion: Such findings suggest that MVE-exposure exacerbates the expression of factors in the CNS associated with AD pathogenesis in aged populations.
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de la Monte Suzanne M., Lyn-Cook Jr. Lascelles E., Lawton Margot, et al. "Hepatic Ceramide May Mediate Brain Insulin Resistance and Neurodegeneration in Type 2 Diabetes and Non-alcoholic Steatohepatitis." In Advances in Alzheimer’s Disease. IOS Press, 2011. https://doi.org/10.3233/978-1-60750-733-8-179.
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Background: Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis (NASH) can lead to cognitive impairment and neurodegeneration. Experimental high fat diet (HFD) induced obesity with T2DM causes neurodegeneration with brain insulin resistance. Objective: Since ceramides are neurotoxic, cause insulin resistance, and are increased in T2DM, we investigated their potential role in neurodegeneration. Methods: C57BL/6 mice were pair-fed HFD or control diets for 4-20 weeks. Pro-ceramide genes and biochemical indices of neurodegeneration were measured. In vitro experiments directly examined neurodegenerative effects of ceramides. Results: Chronic HFD feeding gradually increased body weight, but after 16 weeks, liver weight surged (P&lt;0.001) due to triglyceride accumulation (P&lt;0.001), and brain weight declined (P&lt;0.0001). HFD increased pro-ceramide gene expression in liver (P&lt;0.05-P&lt;0.001), but not brain. Temporal lobes of HFD fed mice had increased ubiquitin (P&lt;0.001) and 4-hydroxynonenal (P&lt;0.05 or P&lt;0.01), and decreased tau, &beta;-actin, and choline acetyltransferase levels (P&lt;0.05-P&lt;0.001) with development of NASH. Ceramide treatment of neuronal cultures caused cell death, oxidative stress, mitochondrial dysfunction, and insulin resistance. Conclusions: In obesity, T2DM, or NASH, excess hepatic production of neurotoxic ceramides that readily cross the blood-brain barrier causes cognitive impairment with brain insulin resistance via a liver-brain axis of neurodegeneration.
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Dymecki, Susan M. "Site-specific recombination in cells and mice." In Gene Targeting. Oxford University Press, 1999. http://dx.doi.org/10.1093/oso/9780199637928.003.0006.
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The use of site-specific recombinase systems has revolutionized our ability to genetically manipulate embryonic stem (ES) cells and mice. Recent advances using the Cre-loxP and Flp-FRT systems have now made it possible to generate ‘clean’ germline mutations following a single gene targeting event, as well as to (in)activate genes in a conditional manner in the living mouse. Not only can target gene mutations be induced in a spatially and temporally restricted fashion, but lineage tracers can be activated in specific progenitor populations to chart cell fate directly in the wild-type or mutant mouse. This chapter introduces site-specific recombination and details a variety of applications, many of which are extensions of the gene targeting vectors and manipulations presented by Hasty et al. in Chapter 1. Many of the mutagenesis techniques which exploit the Cre-loxP system have been compiled earlier in an excellent book by Torres and Kühn (1). In this chapter, I present the Flp-FRT system in addition to the Cre-loxP system, for individual or combined uses. Together, these surveys and protocols should provide a basis for a wide variety of studies on gene function in vivo. As novel recombinase based applications continue to be developed, the possibilities for genome engineering appear without limit. The simplest site-specific recombination systems are comprised of two elements: the recombinase enzyme and a small stretch of DNA specifically recognized by the particular recombinase. These two elements work together to either delete, insert, invert, or translocate associated DNA. Two such recombinase systems have been established in mice (2-5) providing the basic tools for in vivo genetic engineering: the Cre-loxP system from the bacteriophage P1 and the Flp-FRT system from the budding yeast Saccharomyces cerevisiae. Both Cre and Flp are members of the λ integrase superfamily of site-specific recombinases (6) that cleave DNA at a distinct target sequence and then ligate it to the cleaved DNA of a second identical site to generate a contiguous strand. This recombination reaction is carried out with absolute fidelity, such that not a single nucleotide is gained or lost overall, and with no other requirements than the recombinase, the specific target DNA sequence, and some mono- or divalent cations (7).
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"E." In Genetic variants and strains of the Laboratory mouse, edited by Mary F. Lyon, Sohaila Rastan, and S. D. M. Brown. Oxford University PressOxford, 1996. http://dx.doi.org/10.1093/oso/9780198548690.003.0007.
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Abstract This locus is probably homologous with the extension locus which occurs in several other mammals and governs the extension of eumelanin with the opposite effects on phaeomelanin. In this series of alleles, in contrast to those of the agouti locus, the dominant alleles produce partial or full extension of black, the wild-type allele produces normal extension of yellow and black as in the agouti pattern, and the recessive alleles produce partial or full extension of yellow (7). Because the skin cells of e/e mutant mice produce eumelanin after treatment with dibutyryl cyclic AMP, it was suggested that the e locus may control the function of an a-MSH receptor (8). The extension locus has now been shown to encode the receptor for the melanocytestimulating hormone (see below). The semidominant mutations at this locus are all point mutations that result in overactive MSH receptors. (6).
Conference papers on the topic "C57BL/6 wild-type mice"
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Dalenogare, Diéssica Padilha, Diulle Spat Peres, Maria Fernanda Pessano Fialho, and Gabriela Trevisan dos Santos. "Periorbital nociception in a progressive multiple sclerosis mouse model is dependent on TRPA1 channel activation." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.610.
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Background: Headache is one of the main painful symptoms described by multiple sclerosis patients. Previously, it was described that neuropathic pain-like behaviors were dependent on transient receptor potential ankyrin 1 (TRPA1) activation in a progressive multiple sclerosis model induced by experimental autoimmune encephalomyelitis (PMS- EAE) in mice. Objective: Here, we aimed to investigate if periorbital mechanical allodynia induced by PMS-EAE was also related to TRPA1 activation. Design and setting: Federal University of Santa Maria, Santa Maria, RS, Brazil. Methods: To induce a PMS-EAE we used female C57BL/6 wild-type and TRPA1- deficient (Trpa1-/-) mice. By the von Frey test, periorbital mechanical allodynia development was observed, and the nociception peak occurred 14 days after induction. At nociception peak day, the mice were treated with sumatriptan, TRPA1 antagonists (HC-030031, A-967079, metamizole, and propyphenazone. Results: The development of mechanical allodynia was showed as well as the antinociceptive effects for all treatments in induced mice. A significant reduction of TRPA1 expression was detected. Conclusion: Thus, these results suggest that headache-like symptoms induced by the PMS-EAE mouse model might occurring by TRPA1 activation.
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Tur, Dariya, Oleg Shevelev, and Andrey Akulov. "COMPARATIVE MRI STUDY OF THE BRAIN MICE GENETIC LINES: C57BL/6, CD1, NOD.SCID IN A PHARMACOLOGICAL MODEL OF TYPE 1 DIABETES MELLITUS." In XVII INTERNATIONAL INTERDISCIPLINARY CONGRESS NEUROSCIENCE FOR MEDICINE AND PSYCHOLOGY. LCC MAKS Press, 2021. http://dx.doi.org/10.29003/m2354.sudak.ns2021-17/375-376.
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Myers, Kristin M., and Thao D. Nguyen. "Modeling the Inflation Response of C57BL/6 Mouse Sclera." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53181.
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Small rodent models have become increasingly useful to investigate how the mechanical properties of soft tissues may influence disease development. These animal models allow access to aged, diseased, or genetically-altered tissue samples, and through comparisons with wild-type or normal tissue it can be explored how each of these variables influence tissue function. The challenges to deriving meaningful material parameters for these small tissue samples include designing physiologically-relevant mechanical testing protocols and interpreting the experimental load-displacement data in an appropriate constitutive framework to quantify material parameters. This study was motivated by determining the possible role of scleral material properties in the development of glaucomatous damage to the retinal ganglion cells (RGC). Glaucoma is one of the leading causes of blindness in the United States and in the world with an estimate of 60 million people affected by this year [1]. Through exploring mouse models, the overall goal of our work is to determine the role of scleral material properties and scleral tissue microstructure in the pathogenesis of glaucoma.
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Mutoh, Michihiro, Naoya Teraoka, Shinji Takasu, et al. "Abstract 2837: Adiponectin knockout enhances intestinal carcinogenesis in Min and wild-type mice." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-2837.
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Bryan, Andrea, Amy Sung, Ian Lian, and Jeffrey Omens. "The Role of Tropomodulin in Cardiac Function and Remodeling." In ASME 2004 International Mechanical Engineering Congress and Exposition. ASMEDC, 2004. http://dx.doi.org/10.1115/imece2004-61363.
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Tropomodulin is an actin-capping protein in cardiac muscle, and is associated with both sarcomeric and cytoskeletal actin filaments. Homozygous knockout of erythrocyte tropomodulin (E-Tmod) is embryonically lethal, but heterozygous knockout (+/-) mice survive. Heterozygous E-Tmod knockout resulted in smaller right ventricle (RV) cavities and free walls compared to wild type. To investigate the effect of heterozygous tropomodulin knockout on mouse cardiac function and remodeling, mice (n=6 to 9) were subjected to 5 weeks of hypoxia to increase loading conditions on the RV via pulmonary hypertension. The effect of loading was determined by measuring the volume of RV anatomical features, and surface strain during the cardiac cycle. Although there was no significant change due to loading on RV cavity or free wall volume for wild type, geometrical measurements suggest that tissue had been redistributed. Under equal loading conditions, knockout mice exhibited a significant increase in volume for both RV features. RV epicardial function showed an increase in surface area strain at peak systole for hypoxic knockout mice. Thus it appears that heterozygous knockout of E-Tmod affects RV volume under normal and adverse loading conditions, as well as RV function.
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Peterson, Sherket B., Zannatul Ferdous, Magnus Höök, and K. Jane Grande-Allen. "Decorin Deficient Cells Demonstrate Increased Proliferation and Altered Phenotypic Properties." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176043.
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Decorin (DCN), a class I member of the small leucine-rich proteoglycan (SLRP) family, is composed of a protein core of approximately 40kDa [1, 2] substituted with a single glycosaminoglycan (GAG) chain of chondroiton/dermatan sulfate on the N-terminal site [3]. DCN has been reported to interact with collagen [4,5] via its core protein, influence collagen fibrillogenesis [6], and inhibit the growth rates of various cell types when added exogenously to cell cultures [5,6]. There has recently been growing interest and studies in DCN related research using the knockout (KO) mice model which provides an excellent example of inherited disorders that stem from deficiencies in decorin expression [7]. Skin and tendon tissues from DCN KO mice have been characterized as being extremely fragile with significantly reduced strength and stiffness [8, 9]. The DCN KO tissues also show potential functional biglycan compensation [9] and at the microscopic level collagen fibrils with highly irregular diameters, abnormal lateral fusion, and loose packing [6] in contrast to wild type (WT) mice. Despite the intensive investigation of the DCN KO mice, the complexity of the animal model makes it difficult to assess the actual influence of decorin. In an attempt to take a more simplistic approach 2D cell phenotypic characterization studies were performed in addition to studying cell growth, contraction, and matrix organization in 3-D models to show the very distinct biochemical responses to type I collagen when compared to WT control cells.
Reports on the topic "C57BL/6 wild-type mice"
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Ficht, Thomas, Gary Splitter, Menachem Banai, and Menachem Davidson. Characterization of B. Melinensis REV 1 Attenuated Mutants. United States Department of Agriculture, 2000. http://dx.doi.org/10.32747/2000.7580667.bard.
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Brucella Mutagenesis (TAMU) The working hypothesis for this study was that survival of Brucella vaccines was directly related to their persistence in the host. This premise is based on previously published work detailing the survival of the currently employed vaccine strains S19 and Rev 1. The approach employed signature-tagged mutagenesis to construct mutants interrupted in individual genes, and the mouse model to identify mutants with attenuated virulence/survival. Intracellular survival in macrophages is the key to both reproductive disease in ruminants and reticuloendothelial disease observed in most other species. Therefore, the mouse model permitted selection of mutants of reduced intracellular survival that would limit their ability to cause reproductive disease in ruminants. Several classes of mutants were expected. Colonization/invasion requires gene products that enhance host-agent interaction or increase resistance to antibacterial activity in macrophages. The establishment of chronic infection requires gene products necessary for intracellular bacterial growth. Maintenance of chronic infection requires gene products that sustain a low-level metabolism during periods characterized little or no growth (1, 2). Of these mutants, the latter group was of greatest interest with regard to our originally stated premise. However, the results obtained do not necessarily support a simplistic model of vaccine efficacy, i.e., long-survival of vaccine strains provides better immunity. Our conclusion can only be that optimal vaccines will only be developed with a thorough understanding of host agent interaction, and will be preferable to the use of fortuitous isolates of unknown genetic background. Each mutant could be distinguished from among a group of mutants by PCR amplification of the signature tag (5). This approach permitted infection of mice with pools of different mutants (including the parental wild-type as a control) and identified 40 mutants with apparently defective survival characteristics that were tentatively assigned to three distinct classes or groups. Group I (n=13) contained organisms that exhibited reduced survival at two weeks post-infection. Organisms in this group were recovered at normal levels by eight weeks and were not studied further, since they may persist in the host. Group II (n=11) contained organisms that were reduced by 2 weeks post infection and remained at reduced levels at eight weeks post-infection. Group III (n=16) contained mutants that were normal at two weeks, but recovered at reduced levels at eight weeks. A subset of these mutants (n= 15) was confirmed to be attenuated in mixed infections (1:1) with the parental wild-type. One of these mutants was eliminated from consideration due to a reduced growth rate in vitro that may account for its apparent growth defect in the mouse model. Although the original plan involved construction of the mutant bank in B. melitensis Rev 1 the low transformability of this strain, prevented accumulation of the necessary number of mutants. In addition, the probability that Rev 1 already carries one genetic defect increases the likelihood that a second defect will severely compromise the survival of this organism. Once key genes have been identified, it is relatively easy to prepare the appropriate genetic constructs (knockouts) lacking these genes in B. melitensis Rev 1 or any other genetic background. The construction of "designer" vaccines is expected to improve immune protection resulting from minor sequence variation corresponding to geographically distinct isolates or to design vaccines for use in specific hosts. A.2 Mouse Model of Brucella Infection (UWISC) Interferon regulatory factor-1-deficient (IRF-1-/- mice have diverse immunodeficient phenotypes that are necessary for conferring proper immune protection to intracellular bacterial infection, such as a 90% reduction of CD8+ T cells, functionally impaired NK cells, as well as a deficiency in iNOS and IL-12p40 induction. Interestingly, IRF-1-/- mice infected with diverse Brucella abortus strains reacted differently in a death and survival manner depending on the dose of injection and the level of virulence. Notably, 50% of IRF-1-/- mice intraperitoneally infected with a sublethal dose in C57BL/6 mice, i.e., 5 x 105 CFU of virulent S2308 or the attenuated vaccine S19, died at 10 and 20 days post-infection, respectively. Interestingly, the same dose of RB51, an attenuated new vaccine strain, did not induce the death of IRF-1-/- mice for the 4 weeks of infection. IRF-1-/- mice infected with four more other genetically manipulated S2308 mutants at 5 x 105 CFU also reacted in a death or survival manner depending on the level of virulence. Splenic CFU from C57BL/6 mice infected with 5 x 105 CFU of S2308, S19, or RB51, as well as four different S2308 mutants supports the finding that reduced virulence correlates with survival Of IRF-1-/- mice. Therefore, these results suggest that IRF-1 regulation of multi-gene transcription plays a crucial role in controlling B. abortus infection, and IRF-1 mice could be used as an animal model to determine the degree of B. abortus virulence by examining death or survival. A3 Diagnostic Tests for Detection of B. melitensis Rev 1 (Kimron) In this project we developed an effective PCR tool that can distinguish between Rev1 field isolates and B. melitensis virulent field strains. This has allowed, for the first time, to monitor epidemiological outbreaks of Rev1 infection in vaccinated flocks and to clearly demonstrate horizontal transfer of the strain from vaccinated ewes to unvaccinated ones. Moreover, two human isolates were characterized as Rev1 isolates implying the risk of use of improperly controlled lots of the vaccine in the national campaign. Since atypical B. melitensis biotype 1 strains have been characterized in Israel, the PCR technique has unequivocally demonstrated that strain Rev1 has not diverted into a virulent mutant. In addition, we could demonstrate that very likely a new prototype biotype 1 strain has evolved in the Middle East compared to the classical strain 16M. All the Israeli field strains have been shown to differ from strain 16M in the PstI digestion profile of the omp2a gene sequence suggesting that the local strains were possibly developed as a separate branch of B. melitensis. Should this be confirmed these data suggest that the Rev1 vaccine may not be an optimal vaccine strain for the Israeli flocks as it shares the same omp2 PstI digestion profile as strain 16M.
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Splitter, Gary A., Menachem Banai, and Jerome S. Harms. Brucella second messenger coordinates stages of infection. United States Department of Agriculture, 2011. http://dx.doi.org/10.32747/2011.7699864.bard.
Full textAbstract:
Aim 1: To determine levels of this second messenger in: a) B. melitensiscyclic-dimericguanosinemonophosphate-regulating mutants (BMEI1448, BMEI1453, and BMEI1520), and b) B. melitensis16M (wild type) and mutant infections of macrophages and immune competent mice. (US lab primary) Aim 2: To determine proteomic differences between Brucelladeletion mutants BMEI1453 (high cyclic-dimericguanosinemonophosphate, chronic persistent state) and BMEI1520 (low cyclicdimericguanosinemonophosphate, acute virulent state) compared to wild type B. melitensisto identify the role of this second messenger in establishing the two polar states of brucellosis. (US lab primary with synergistic assistance from the Israel lab Aim 3: Determine the level of Brucellacyclic-dimericguanosinemonophosphate and transcriptional expression from naturally infected placenta. (Israel lab primary with synergistic assistance from the US lab). B. Background Brucellaspecies are Gram-negative, facultative intracellular bacterial pathogens that cause brucellosis, the most prevalent zoonosis worldwide. Brucellosis is characterized by increased abortion, weak offspring, and decreased milk production in animals. Humans are infected with Brucellaby consuming contaminated milk products or via inhalation of aerosolized bacteria from occupational hazards. Chronic human infections can result in complications such as liver damage, orchitis, endocarditis, and arthritis. Brucellaspp. have the ability to infect both professional and non-professional phagocytes. Because of this, Brucellaencounter varied environments both throughout the body and within a cell and must adapt accordingly. To date, few virulence factors have been identified in B. melitensisand even less is known about how these virulence factors are regulated. Subsequently, little is known about how Brucellaadapt to its rapidly changing environments, and how it alternates between acute and chronic virulence. Our studies suggest that decreased concentrations of cyclic dimericguanosinemonophosphate (c-di-GMP) lead to an acute virulent state and increased concentrations of c-di-GMP lead to persistent, chronic state of B. melitensisin a mouse model of infection. We hypothesize that B. melitensisuses c-di-GMP to transition from the chronic state of an infected host to the acute, virulent stage of infection in the placenta where the bacteria prepare to infect a new host. Studies on environmental pathogens such as Vibrio choleraeand Pseudomonas aeruginosasupport a mechanism where changes in c-di-GMP levels cause the bacterium to alternate between virulent and chronic states. Little work exists on understanding the role of c-di-GMP in dangerous intracellular pathogens, like Brucellathat is a frequent pathogen in Israeli domestic animals and U.S. elk and bison. Brucellamust carefully regulate virulence factors during infection of a host to ensure proper expression at appropriate times in response to host cues. Recently, the novel secondary signaling molecule c-di-GMP has been identified as a major component of bacterial regulation and we have identified c-di-GMP as an important signaling factor in B. melitensishost adaptation. C. Major conclusions, solutions, achievements 1. The B. melitensis1453 deletion mutant has increased c-di-GMP, while the 1520 deletion mutant has decreased c-di-GMP. 2. Both mutants grow similarly in in vitro cultures; however, the 1453 mutant has a microcolony phenotype both in vitro and in vivo 3. The 1453 mutant has increased crystal violet staining suggesting biofilm formation. 4. Scanning electron microscopy revealed an abnormal coccus appearance with in increased cell area. 5. Proteomic analysis revealed the 1453 mutant possessed increased production of proteins involved in cell wall processes, cell division, and the Type IV secretion system, and a decrease in proteins involved in amino acid transport/metabolism, carbohydrate metabolism, fatty acid production, and iron acquisition suggesting less preparedness for intracellular survival. 6. RNAseq analysis of bone marrow derived macrophages infected with the mutants revealed the host immune response is greatly reduced with the 1453 mutant infection. These findings support that microlocalization of proteins involved in c-di-GMP homeostasis serve a second messenger to B. melitensisregulating functions of the bacteria during infection of the host.