Phenotypes for Tg(Myh6-MYL2*R58Q)#Dsc MGI:5904628 MGI Mouse

cardiovascular system

abnormal myocardial fiber morphology ( J:144685 )

• myofibrillar disarray and some abnormal clustering of nuclei in the hearts of older mice

abnormal cardiovascular system physiology ( J:162200 )

• decrease in cardiac function in isolated perfused working hearts

• cardiac output, cardiac work, and cardiac power are decreased in aerobically perfused and spontaneously beating hearts to a higher extent than in Tg(Myh6-MYL7*N47K)#Dsc /0 mice

• cardiac efficiency (ratio of cardiac power to oxygen consumption) is decreased during the initial aerobic perfusion period and after ischemia during reperfusion

• however, no differences in heart rate, left ventricle end-systolic or end-diastolic wall thickness, left ventricular mass and left ventricle ejection fraction

decreased cardiac output ( J:162200 )

• cardiac output is decreased in aerobically perfused and spontaneously beating hearts

abnormal diastolic filling velocity ( J:162200 )

• alterations in diastolic transmitral velocities and deceleration time in myocardium indicating early diastolic dysfunction

• 30% increase in inter-ventricular septal thickness in diastole and posterior wall thickness in diastole at 15 months of age

abnormal cardiac muscle contractility ( J:162200 )

• increase in calcium-sensitivity of contraction

decreased cardiac muscle relaxation ( J:162200 )

• slower muscle relaxation

abnormal myocardial fiber physiology ( J:144685 , J:162200 )

• the duration of calcium concentration transients in papillary muscles is 25% longer than in wild-type mice (J:144685)

• force transients are prolonged and there is an increase in steady-state force in papillary muscle fibers (J:144685)

• calcium sensitivity of ATPase activity is increased in papillary muscle fibers (J:144685)

• however, the energy cost of rate of dissociation of force generating myosin cross-bridge plotted as a function of activation state is the same as in wild-type fibers (J:144685)

• increase in calcium-sensitivity of ATPase in myofibrils (J:162200)

• myocardium shows a largely increased ATPase activity at low calcium concentrations (J:162200)

• the level of myofibrillar ATPase activity in myofibrils is higher at submaximal calcium concentrations while no difference is seen at saturating calcium concentrations (J:162200)

• poor myofibrillar ATPase cooperativity (J:162200)

abnormal response to cardiac infarction ( J:162200 )

• poor recovery after acute ischemic episode

homeostasis/metabolism