Phenotypes Associated with This Genotype

Genotype
MGI:7662823

• Allelic Composition: Trim29^{tm1c(EUCOMM)Wtsi}/Trim29^{tm1c(EUCOMM)Wtsi}; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * C57BL/6NTac
• Cell Lines: EPD0439_4_D01

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

decreased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:349246 )

♂ • following i.p. infection with Coxsackievirus B3 (CVB3, strain Nancy), mice show significantly improved survival rates relative to CVB3-infected controls

immune system

increased T cell proliferation ( J:349246 )

♂ • when myeloid-derived suppressor cells (MDSCs) from 3-day CVB3-infected hearts are cocultured with negatively selected CD3+ T cells and stimulated with anti-CD3 and anti-CD28 antibodies, the % of proliferating CD8+ T cells is significantly higher than that in controls

increased interferon level ( J:349246 )

♂ • following CVB3 infection, mice show significantly higher IFN-alpha and IFN-beta levels in the heart than CVB3-infected controls

decreased interleukin level ( J:349246 )

♂ • following CVB3 infection, mice show significantly lower IL-6 and IL-1beta levels in the heart than CVB3-infected controls

abnormal tumor necrosis factor level ( J:349246 )

♂ • following CVB3 infection, mice show significantly lower TNF levels in the heart than CVB3-infected controls

increased interferon-gamma secretion ( J:349246 )

♂ • upon in vitro stimulation with PMA/ionomycin, CD8+ T cells show a significantly enhanced IFN-gamma producing ability in the heart and spleen from 2-day CVB3-infected mice

♂ • however, the IFN-gamma-producing ability of CD8+ T cells in spleen is similar to that in untreated controls before CVB3 infection

decreased inflammatory response ( J:349246 )

♂ • 2 days after CVB3 infection, mice show significantly lower cell numbers of monocytic MDSCs (CD11b+Ly6C+Ly6G-), macrophages, neutrophils, B cells and T cells infiltrated in the heart than CVB3-infected controls

decreased susceptibility to Picornaviridae infection ( J:349246 )

♂ • following i.p. infection with Coxsackievirus B3 (CVB3, strain Nancy), mice show significantly less inflammation and infiltration of inflammatory cells in heart, lower heart weight/baseline body weight, improved cardiac function (as assessed by ejection fraction and fractional shortening), reduced viral titers in heart, pancreas and spleen homogenates, and lower levels of cardiac inflammatory cytokines (IL-6, IL-1beta, and TNF) than CVB3-infected controls, indicating protection from viral myocarditis

decreased susceptibility to Picornaviridae infection induced morbidity/mortality ( J:349246 )

♂ • following i.p. infection with Coxsackievirus B3 (CVB3, strain Nancy), mice show significantly improved survival rates relative to CVB3-infected controls

cellular

decreased fetal cardiomyocyte apoptosis ( J:349246 )

♂ • in vitro, primary neonatal cardiomyocytes infected with CVB3 show dramatically reduced expression of CHOP, cleaved caspase-3, and BAX, indicating reduced EIF2AK3-mediated ER stress and apoptosis

increased T cell proliferation ( J:349246 )

♂ • when myeloid-derived suppressor cells (MDSCs) from 3-day CVB3-infected hearts are cocultured with negatively selected CD3+ T cells and stimulated with anti-CD3 and anti-CD28 antibodies, the % of proliferating CD8+ T cells is significantly higher than that in controls

decreased endoplasmic reticulum stress ( J:349246 )

♂ • following infection with CVB3, primary neonatal cardiomyocytes from 2-day-old mice show dramatically reduced phosphorylation of EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3, also known as PERK), suggesting reduced EIF2AK3-mediated ER stress

homeostasis/metabolism

decreased circulating creatine kinase level ( J:349246 )

♂ • following CVB3 infection, mice show dramatically reduced circulating creatine kinase levels relative to CVB3-infected controls

increased interferon level ( J:349246 )

♂ • following CVB3 infection, mice show significantly higher IFN-alpha and IFN-beta levels in the heart than CVB3-infected controls

decreased interleukin level ( J:349246 )

♂ • following CVB3 infection, mice show significantly lower IL-6 and IL-1beta levels in the heart than CVB3-infected controls

abnormal tumor necrosis factor level ( J:349246 )

♂ • following CVB3 infection, mice show significantly lower TNF levels in the heart than CVB3-infected controls

hematopoietic system

increased T cell proliferation ( J:349246 )

♂ • when myeloid-derived suppressor cells (MDSCs) from 3-day CVB3-infected hearts are cocultured with negatively selected CD3+ T cells and stimulated with anti-CD3 and anti-CD28 antibodies, the % of proliferating CD8+ T cells is significantly higher than that in controls

decreased myeloid cell number ( J:349246 )

♂ • 2 days after CVB3 infection, mice show a significantly lower frequency of myeloid-derived suppressor cells (CD11b+ Gr1+ MDSCs) in the heart and spleen than CVB3-infected controls

♂ • however, the frequency of MDSCs in spleen is similar to that in untreated controls before CVB3 infection

cardiovascular system

decreased fetal cardiomyocyte apoptosis ( J:349246 )

♂ • in vitro, primary neonatal cardiomyocytes infected with CVB3 show dramatically reduced expression of CHOP, cleaved caspase-3, and BAX, indicating reduced EIF2AK3-mediated ER stress and apoptosis

muscle

decreased fetal cardiomyocyte apoptosis ( J:349246 )

♂ • in vitro, primary neonatal cardiomyocytes infected with CVB3 show dramatically reduced expression of CHOP, cleaved caspase-3, and BAX, indicating reduced EIF2AK3-mediated ER stress and apoptosis