Phenotypes Associated with This Genotype

Genotype
MGI:5313516

• Allelic Composition: Tg(Myh6-Actc1*R312H)307Iko/?
• Genetic Background: involves: C57BL/6

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

mortality/aging

premature death ( J:178587 )

• mutants die by 35 weeks of age due to heart failure

cardiovascular system

myocardial fiber degeneration ( J:178587 )

• degenerated cardiomyocytes with an increase in vacuolar formation and lysis of myofibrils

enlarged heart ( J:178587 )

increased heart weight ( J:178587 )

• increase in heart weight and ratio of heart weight to body weight

dilated heart left ventricle ( J:178587 )

• left ventricular dimension is gradually increased

cardiac fibrosis ( J:178587 )

• cardiac fibrosis is seen at 10 months of age

abnormal cardiovascular system physiology ( J:178587 )

• 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

dilated cardiomyopathy ( J:178587 )

• decrease in cardiac systolic function at 10 months of age

decreased cardiac muscle contractility ( J:178587 )

• fractional shortening is reduced

increased heart rate ( J:178587 )

decreased QRS amplitude ( J:178587 )

• ECG indicates low amplitude of the R wave

abnormal myocardial fiber physiology ( J:178587 )

• 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

cellular

increased cardiomyocyte apoptosis ( J:178587 )

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

muscle

myocardial fiber degeneration ( J:178587 )

• degenerated cardiomyocytes with an increase in vacuolar formation and lysis of myofibrils

dilated cardiomyopathy ( J:178587 )

• decrease in cardiac systolic function at 10 months of age

decreased cardiac muscle contractility ( J:178587 )

• fractional shortening is reduced

increased cardiomyocyte apoptosis ( J:178587 )

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

growth/size/body

enlarged heart ( J:178587 )

increased heart weight ( J:178587 )

• increase in heart weight and ratio of heart weight to body weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1R		DOID:0110456	OMIM:613424	J:178587