Phenotypes Associated with This Genotype

Genotype
MGI:5905194

• Allelic Composition: Tg(Myh6-Des*)641Rbns/0
• Genetic Background: involves: FVB/N

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

cardiovascular system

abnormal myocardial fiber morphology ( J:108730 )

• cardiomyocytes contain aberrant intrasarcoplasmic and electron-dense granular filamentous aggregates that are desmin-positive

• the desmin filament network is disrupted

• myofibril alignment is perturbed at the Z line

• concentric hypertrophy of cardiomyocytes in both ventricles

• however, sarcomere length and myocyte length are normal in both ventricles

increased myocardial fiber size ( J:108730 )

• cardiomyocyte size is increased due to increases in the transverse sectional area

cardiac hypertrophy ( J:108730 )

• the ratio of ventricle to body weight is increased and most pronounced between 4 to 8 weeks of age and is progressively ameliorated in the adult

decreased ventricle muscle contractility ( J:108730 )

• left ventricular systolic function is affected, with dP/dt(max) decreased indicating that rate of ventricular contraction is decreased

• response of myocardial fibers to the beta-agonist dobutamine is blunted

abnormal cardiac muscle relaxation ( J:108730 )

• left ventricular diastolic function is compromised, with left ventricle minimum dP/dt higher under baseline conditions compared with controls

• the time constant of relaxation is prolonged both at baseline and during dobutamine stimulation

abnormal heart echocardiography feature ( J:108730 )

• echocardiography shows an increase in posterior wall thickness but absence of changes in diastolic and systolic left ventricular chamber dimensions

increased left ventricle diastolic pressure ( J:108730 )

• baseline left ventricular end-diastolic pressure is elevated

abnormal myocardial fiber physiology ( J:108730 )

• isolated cardiomyocytes form 8-10 week old mice exhibit compromised contractile and relaxation functions, with percent shortening of unloaded myocytes decreased by 38% and first derivatives of both shortening and relengthening are decreased by 42% and 35%, respectively

muscle

abnormal myocardial fiber morphology ( J:108730 )

• cardiomyocytes contain aberrant intrasarcoplasmic and electron-dense granular filamentous aggregates that are desmin-positive

• the desmin filament network is disrupted

• myofibril alignment is perturbed at the Z line

• concentric hypertrophy of cardiomyocytes in both ventricles

• however, sarcomere length and myocyte length are normal in both ventricles

increased myocardial fiber size ( J:108730 )

• cardiomyocyte size is increased due to increases in the transverse sectional area

decreased ventricle muscle contractility ( J:108730 )

• left ventricular systolic function is affected, with dP/dt(max) decreased indicating that rate of ventricular contraction is decreased

• response of myocardial fibers to the beta-agonist dobutamine is blunted

abnormal cardiac muscle relaxation ( J:108730 )

• left ventricular diastolic function is compromised, with left ventricle minimum dP/dt higher under baseline conditions compared with controls

• the time constant of relaxation is prolonged both at baseline and during dobutamine stimulation

abnormal Z line morphology ( J:108730 )

• Z-band alignment is perturbed in cardiomyocytes

growth/size/body

cardiac hypertrophy ( J:108730 )

• the ratio of ventricle to body weight is increased and most pronounced between 4 to 8 weeks of age and is progressively ameliorated in the adult

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myofibrillar myopathy 1		DOID:0080092	OMIM:601419	J:108730