Mouse Genome Informatics
tg
    Tg(Myh6-Actc1*R312H)307Iko/?
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• mutants die by 35 weeks of age due to heart failure

cardiovascular system
• degenerated cardiomyocytes with an increase in vacuolar formation and lysis of myofibrils
• increase in heart weight and ratio of heart weight to body weight
• left ventricular dimension is gradually increased
• cardiac fibrosis is seen at 10 months of age
• treatment of mutants with bisoprolol, a beta-blocker, ameliorates cardiac dysfunction
• treatment of mutants with KN-93, a CAMKII inhibitor, prevents left ventricular dilatation and preserves cardiac function
• decrease in cardiac systolic function at 10 months of age
• fractional shortening is reduced
• ECG indicates low amplitude of the R wave
• ECG does not show life-threatening arrhythmias, however spontaneous calcium sparks and calcium waves are increased in cardiomyocytes
• myofilaments exhibit a decrease in calcium sensitivity of force generation to a similar extent at both 2 and 10 months of age
• hearts show an increase in apoptotic cardiomyocytes at 5 months of age

cellular
• hearts show an increase in apoptotic cardiomyocytes at 5 months of age

muscle
• degenerated cardiomyocytes with an increase in vacuolar formation and lysis of myofibrils
• decrease in cardiac systolic function at 10 months of age
• fractional shortening is reduced
• hearts show an increase in apoptotic cardiomyocytes at 5 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Cardiomyopathy, Dilated, 1r; CMD1R 613424 J:178587