Phenotypes Associated with This Genotype

Genotype
MGI:5906020

• Allelic Composition: Tg(Myh6-Tpm1*E54K)67Dfw/0
• Genetic Background: involves: FVB/N

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

mortality/aging

premature death ( J:137813 )

• mice start dying by 4-6 months of age, with 38% dying by 8 months of age

cardiovascular system

abnormal myocardial fiber morphology ( J:137813 )

• mild disorganization of the myocytes at the base of the ventricles

increased myocardial fiber size ( J:137813 )

• hearts show mild myocyte hypertrophy at 2 months of age

increased heart weight ( J:137813 )

• despite the increase in body weight by 5 months, the heart weight to body weight ratio is still increased

dilated heart ventricle ( J:137813 )

• by 5 months, mice develop significant dilation of both ventricles

cardiac interstitial fibrosis ( J:137813 )

• hearts show very mild interstitial fibrosis after 2 months of age

dilated cardiomyopathy ( J:137813 )

• mice tend to develop dilated cardiomyopathy after 2 months of age

• mice that survive beyond 8 months develop dilated cardiomyopathy

• mice show an upregulation of molecular markers of cardiomyopathy at 5 months of age

decreased cardiac output ( J:137813 )

• cardiac output is reduced in 5 month old mice

• however, heart rate is unaffected

decreased cardiac muscle contractility ( J:137813 )

• 3 month old hearts ex vivo show reduced rates of relaxation and contraction with increased time to peak pressure and half-time to relaxation

decreased ventricle muscle contractility ( J:137813 )

• hearts show increased left ventricle diastolic and systolic diameter and a reduction in the left ventricle fractional shortening in 5 month old mice

decreased cardiac muscle relaxation ( J:137813 )

• 3 month old hearts ex vivo show reduced rates of relaxation and contraction with increased time to peak pressure and half-time to relaxation

decreased left ventricle diastolic pressure ( J:137813 )

• end-diastolic and diastolic pressures are increased in 3 month old hearts ex vivo

decreased left ventricle systolic pressure ( J:137813 )

• systolic pressure is decreased in 3 month old hearts ex vivo

abnormal myocardial fiber physiology ( J:137813 )

• skinned left ventricular fiber bundles from 5 month old mice show a severe depression in maximum tension and a decrease in myofilament calcium sensitivity

congestive heart failure ( J:137813 )

growth/size/body

increased heart weight ( J:137813 )

• despite the increase in body weight by 5 months, the heart weight to body weight ratio is still increased

increased body weight ( J:137813 )

• about 50% increase in body weight by 5 months of age, most likely attributable to edema

homeostasis/metabolism

edema ( J:137813 )

• peripheral edema by 5 months of age

• however, no ascites formation is seen and lung weight is normal

decreased physiological sensitivity to xenobiotic ( J:137813 )

• hearts show a blunted response to lower concentrations of isoproterenol, a beta-adrenergic agonist, however a steep increase in performance is seen at higher concentrations of isoproterenol, restoring normal cardiac function

muscle

abnormal myocardial fiber morphology ( J:137813 )

• mild disorganization of the myocytes at the base of the ventricles

increased myocardial fiber size ( J:137813 )

• hearts show mild myocyte hypertrophy at 2 months of age

dilated cardiomyopathy ( J:137813 )

• mice tend to develop dilated cardiomyopathy after 2 months of age

• mice that survive beyond 8 months develop dilated cardiomyopathy

• mice show an upregulation of molecular markers of cardiomyopathy at 5 months of age

decreased cardiac muscle contractility ( J:137813 )

• 3 month old hearts ex vivo show reduced rates of relaxation and contraction with increased time to peak pressure and half-time to relaxation

decreased ventricle muscle contractility ( J:137813 )

• hearts show increased left ventricle diastolic and systolic diameter and a reduction in the left ventricle fractional shortening in 5 month old mice

decreased cardiac muscle relaxation ( J:137813 )

• 3 month old hearts ex vivo show reduced rates of relaxation and contraction with increased time to peak pressure and half-time to relaxation

respiratory system

abnormal bronchiole morphology ( J:137813 )

• moderate diffuse peribronchiolar neutrophil cuffing is seen in the lungs by 5 months of age

cellular

cardiac interstitial fibrosis ( J:137813 )

• hearts show very mild interstitial fibrosis after 2 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1Y		DOID:0110457	OMIM:611878	J:137813