Phenotypes Associated with This Genotype

Genotype
MGI:6256757

• Allelic Composition: Tg(Myh6-Tpm1*D230N)HJcf/0
• Genetic Background: B6.FVB-Tg(Myh6-Tpm1*D230N)HJcf

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

cardiovascular system

abnormal intercalated disk morphology ( J:243724 )

• hearts show broadened intercalated discs

increased heart weight ( J:243724 )

• heart weight to body weight measurements show that cardiac remodeling is seen as early as 2 months of age, and increased heart weight/body weight ratio is significant at 6 months

• however, inflammatory infiltration into hearts is not seen at 6 months and no myocardial fibrosis is detected

dilated heart left ventricle ( J:243724 )

• left ventricles are dilated in 6 month old mice

dilated cardiomyopathy ( J:243724 )

decreased cardiac muscle contractility ( J:243724 )

• decrease in contractile function of hearts, with decreased ejection fraction and percent fractional shortening

• however, cardiac output is normal

decreased ventricle muscle contractility ( J:243724 )

• pressure volume loop recordings show that left ventricular contractile function is decreased with no effect on relaxation, with decreased slope of the end systolic pressure-volume relationship and dPmax and increased end systolic volume and end diastolic volume, indicating a loss of contractile reserve

abnormal heart echocardiography feature ( J:243724 )

• echocardiography at 6 months indicates increased left ventricular chamber size, increased diastolic and systolic left ventricular internal diameters, increased end diastolic volume and end systolic volume, and decreased ejection fraction and percent fractional shortening

abnormal myocardial fiber physiology ( J:243724 )

• isolated myocytes show increased rates of contraction and relaxation

• isolated myocytes show increased peak amplitude calcium transients and greater rates of calcium rise and fall at baseline

• the increase in rate of contraction and relaxation and increase in rate of calcium transients is less pronounced in myocytes stimulated with isoproterenol (beta-adrenergic stimulation) compared to controls

• myofilaments exhibit a reduced calcium sensitivity of sliding velocity

muscle

abnormal intercalated disk morphology ( J:243724 )

• hearts show broadened intercalated discs

dilated cardiomyopathy ( J:243724 )

decreased cardiac muscle contractility ( J:243724 )

• decrease in contractile function of hearts, with decreased ejection fraction and percent fractional shortening

• however, cardiac output is normal

decreased ventricle muscle contractility ( J:243724 )

• pressure volume loop recordings show that left ventricular contractile function is decreased with no effect on relaxation, with decreased slope of the end systolic pressure-volume relationship and dPmax and increased end systolic volume and end diastolic volume, indicating a loss of contractile reserve

growth/size/body

increased heart weight ( J:243724 )

• heart weight to body weight measurements show that cardiac remodeling is seen as early as 2 months of age, and increased heart weight/body weight ratio is significant at 6 months

• however, inflammatory infiltration into hearts is not seen at 6 months and no myocardial fibrosis is detected

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1Y		DOID:0110457	OMIM:611878	J:243724