Mouse Genome Informatics
ht
    Myh6tm3.1Jse/Myh6+
involves: 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
cardiovascular system
• at 35 weeks but not prior to 20 weeks
• cyclosporine A treatment accelerates development of increased left ventricular wall thickness (1.8-fold) unlike similarly treated wild-type mice
• mice treated with cyclosporine A and Tgf-beta neutralizing antibodies exhibit less maximal left ventricular wall thickness compared with mice treated with cyclosporine A and IgG
• mice treated with cyclosporin A and losartan exhibit less maximal left ventricular wall thickness compared with mice treated with only cyclosporin
• however, mice treated with cyclosporin A and losartan exhibit the same maximal left ventricular wall thickness as in similarly treated wild-type mice
• cyclosporine A treatment accelerates development of myocardial fibrosis (80-fold) unlike similarly treated wild-type mice
• mice treated with cyclosporine A and Tgf-beta neutralizing antibodies exhibit reduced cardiac fibrosis compared with mice treated with cyclosporine A and IgG
• mice treated with cyclosporin A and losartan exhibit 2.9-fold less fibrosis compared with mice treated with only cyclosporin A
• non-myocyte cells from hypertrophic mice treated with cyclosporine A exhibit a 4-fold increase in proliferation compared with cells from similarly treated wild-type mice
• non-myocyte cells in regions with normal histological architecture from hypertrophic mice treated with cyclosporine A exhibit a 3.3-fold increase in proliferation compared with cells from similarly treated wild-type mice
• non-myocyte cells in left ventricular sections with focal fibrosis or overt interstitial expansion from hypertrophic mice treated with cyclosporine A exhibit a 4-fold increase in proliferation compared with cells from similarly treated wild-type mice
• proliferation of non-myocyte cells is greater in regions with focal fibrosis and expanded interstitium compared to in regions with normal architecture
• mice treated with cyclosporine A and Tgf-beta neutralizing antibodies exhibit reduced non-myocyte proliferation in regions with fibrosis and regions with preserved myocardial architecture compared with mice treated with cyclosporine A and IgG
• mice treated with cyclosporin A and losartan exhibit reduced non-myocyte cell proliferation in fibrotic regions (8-fold) and regions with preserved myocardial architecture compared with mice treated with mice treated with only cyclosporin A
• however, losartan treatment reduces proliferation in the hypertrophic hearts of mice treated with cyclosporin A to the level observed in similarly treated wild-type mice
• mice exhibit hypertrophic cardiomyopathy at 35 weeks but not prior to 20 weeks
• cyclosporine A treatment accelerates development hypertrophic cardiomyopathy histopathology unlike similarly treated wild-type mice

homeostasis/metabolism
• cyclosporine A-treated mice accelerates increased left ventricular wall thickness (1.8-fold), overt hypertrophic cardiomyopathy histopathology, including myocardial fibrosis (80-fold), and preserved cardiac function unlike similarly treated wild-type mice

muscle
• mice exhibit hypertrophic cardiomyopathy at 35 weeks but not prior to 20 weeks
• cyclosporine A treatment accelerates development hypertrophic cardiomyopathy histopathology unlike similarly treated wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Cardiomyopathy, Familial Hypertrophic, 14; CMH14 613251 J:165269