All Phenotypes Tg(Myh6-Myl2*)21Rbns MGI Mouse

abnormal myocardial fiber morphology ( J:114298 )

• cardiomyocytes are irregularly shaped, show the presence of vacuoles, have an irregular distribution of mitochondria and develop myofibril degeneration

• sarcomeric organization is lost, the intercalated discs are convoluted, large interstitial spaces separate the myocytes and there is increased collagen deposition

abnormal intercalated disk morphology ( J:114298 )

• intercalated discs are convoluted in cardiomyocytes

myocardial fiber degeneration ( J:114298 )

• cardiomyoctyes develop myofibril degeneration

increased heart atrium size ( J:114298 )

• biatrial hypertrophy

dilated heart atrium ( J:114298 )

abnormal heart septum morphology ( J:114298 )

• show a trend toward septal hypertrophy at 10 weeks of age, however left ventricle free wall weights are unaffected

cardiac hypertrophy ( J:114298 )

• exhibit biatrial hypertrophy, a trend toward septal hypertrophy and activation of hypertrophic markers

dilated heart right ventricle ( J:114298 )

• seen at 16 weeks of age

abnormal cardiovascular system physiology ( J:114298 )

abnormal cardiac muscle contractility ( J:114298 )

• the response of dP/dt_max to beta-adrenergic stimulation is significantly reduced, although heart rate is not affected

decreased cardiac muscle contractility ( J:110993 )

• perfused hearts consistently show decreased contractility throughout the range of frequencies tested, however show no differences in the force-frequency relation in papillary muscles, the pressure-frequency relation in Langendorff perfused hearts, or shortening-frequency relation of isolated cardiac myocytes

abnormal cardiac muscle relaxation ( J:114298 )

• the absolute values of dP/dt_min are lower under both nonstimulated conditions and at all levels of beta-adrenergic stimulation, however no differences are seen in mean arterial pressure and left ventricular end diastolic pressure

tricuspid valve regurgitation ( J:114298 )

• severe tricuspid valve insufficiency as evidenced by the regurgitation jet in 16 week old mutants

decreased left ventricle developed pressure ( J:110993 )

• perfused hearts show a reduction in left ventricular developed pressure of about 20 mmHg at the median frequency (450 bpm) tested

abnormal myocardial fiber physiology ( J:114298 )

• force production of fibers in response to increasing calcium levels is normal under dephosphorylated conditions, however after myosin light chain kinase treatment to induce phosphorylation, mutants do not show an increase in calcium sensitivity (no leftward shift in the force-calcium curve) as is seen in controls

decreased systemic arterial systolic blood pressure ( J:110993 )

• perfused hearts consistently develop a reduced systolic pressure at all the frequencies of stimulation tested