Phenotypes Associated with This Genotype

Genotype
MGI:6193978

• Allelic Composition: Tg(Myh6-MYL2*K104E)2Dsc/0
• Genetic Background: involves: C57BL/6 * SJL

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

cardiovascular system

abnormal heart morphology ( J:263776 )

• hearts of both young and old mice exhibit increased mitochondria

• however, sarcomeric structure in the myocardium at 6 months of age is normal

cardiac hypertrophy ( J:263776 )

• mice aged over 13 months exhibit hypertrophy of both anterior and posterior wall and an approximate 1.6-fold higher left ventricle mass indicating that cardiac hypertrophy develops in senescent mice

• hypertrophic phenotype in old mice shows a concentric pattern manifested by reduced left ventricle diameter in systole and diastole

cardiac fibrosis ( J:263776 )

• mild fibrosis is seen at 8 months of age which severely increases in 15 month old mice

increased cardiac muscle contractility ( J:263776 )

• the ejection fraction is higher in older mice, indicating that hypertrophy does not compromise systolic function

decreased cardiac muscle relaxation ( J:263776 )

• 6 month old mice show a prolonged isovolumic relaxation time (Tau) and a tendency for slower rate of pressure decline, indicating diastolic function alterations

• mice show mild signs of diastolic disturbance with lower E/A ratios at 6 months of age

• however, mice show preserved systolic function at 6 months of age

abnormal heart echocardiography feature ( J:263776 )

• echocardiography with pulse wave Doppler shows diastolic disturbance with reduced E/A transmitral velocities ratio in 6 month old mice

abnormal myocardial fiber physiology ( J:263776 )

• skinned papillary muscles from 5-6 month old mice show reduced maximal tension and slower muscle relaxation rates

• skinned papillary muscle shows increased levels of passive tension suggesting an increase in muscle stiffness in the myocardium

• myofibril myosin cross-bridges show an increase in the rate of biding to thin filaments and a faster rate of power stroke and decrease in the rate of transition to a rigor-like state, suggesting that cross-bridges stay attached longer to actin and relaxation takes a longer time to be completed

• myosin ATPase activity is higher, indicating increased energy consumption

• in in vitro motility assay, myosin produces higher actin sliding velocity under zero load but velocity decreases with applied load

cardiomyopathy ( J:263776 )

• echocardiography of old mice indicates hypertrophic cardiomyopathy

cellular

increased mitochondrial number ( J:263776 )

• hearts of both young and old mice exhibit increased mitochondria

muscle

increased cardiac muscle contractility ( J:263776 )

• the ejection fraction is higher in older mice, indicating that hypertrophy does not compromise systolic function

decreased cardiac muscle relaxation ( J:263776 )

• 6 month old mice show a prolonged isovolumic relaxation time (Tau) and a tendency for slower rate of pressure decline, indicating diastolic function alterations

• mice show mild signs of diastolic disturbance with lower E/A ratios at 6 months of age

• however, mice show preserved systolic function at 6 months of age

cardiomyopathy ( J:263776 )

• echocardiography of old mice indicates hypertrophic cardiomyopathy

growth/size/body

cardiac hypertrophy ( J:263776 )

• mice aged over 13 months exhibit hypertrophy of both anterior and posterior wall and an approximate 1.6-fold higher left ventricle mass indicating that cardiac hypertrophy develops in senescent mice

• hypertrophic phenotype in old mice shows a concentric pattern manifested by reduced left ventricle diameter in systole and diastole

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 10		DOID:0110316	OMIM:608758	J:263776