Phenotypes Associated with This Genotype

Genotype
MGI:5906193

• Allelic Composition: Tg(Myh6-Tnni3*)1Ammu/0
• Genetic Background: involves: A/J * C57BL/6

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

cardiovascular system

abnormal myocardium layer morphology ( J:59433 )

• mice exhibit stunned myocardium

enlarged heart ( J:59433 )

• cardiac enlargement

• however, heart walls are not atrophied and myocellular architecture is normal

increased heart weight ( J:59433 )

• modest increase in heart-to-body weight ratio

dilated heart ventricle ( J:59433 )

• echocardiography indicates ventricular chamber dilatation

dilated heart left ventricle ( J:59433 , J:104770 )

• allopurinol treatment prevents left ventricular dilation (J:104770)

dilated cardiomyopathy ( J:104770 )

• 15% increase in left ventricular end-diastolic dimension, 32% increase in left ventricular end-systolic dimension, and a 15% decrease in fractional shortening

decreased cardiac muscle contractility ( J:59433 , J:104770 )

• systolic function is depressed as indicated by a decrease in the rate of pressure development (dP/dt max) and by reductions in the load-independent indices of preload-recruitable stroke work and end-systolic elastance (J:59433)

• 15% decrease in fractional shortening (J:104770)

• oral treatment with allopurinol at an early stage improves cardiac contractility (J:104770)

abnormal cardiac muscle relaxation ( J:59433 )

• diastolic relaxation is slowed

• mice exhibit a blunted effect of adrenergic stimulation with isoproterenol on ventricular relaxation

abnormal heart echocardiography feature ( J:59433 , J:104770 )

• end diastolic dimension of the left ventricular chamber is increased (J:59433)

• 15% increase in left ventricular end-diastolic dimension, 32% increase in left ventricular end-systolic dimension, and a 15% decrease in fractional shortening (J:104770)

• mice treated with allopurinol show normal left ventricular end-diastolic dimension over the 2 months of treatment (J:104770)

decreased heart rate ( J:59433 )

• heart rate is slightly slower

abnormal myocardial fiber physiology ( J:59433 , J:104770 )

• ventricular trabecular muscle exhibits a decrease of maximal calcium-activated force and a rightward shift in the force-calcium relationship (J:59433)

• however, calcium transients are not reduced in cardiac muscles (J:59433)

• 40% reduction in developed twitch tension in isolated cardiac muscle over a rage of calcium values (J:104770)

• allopurinol treatment restores developed twitch tension to 70% of that in controls (J:104770)

• oxidation of myofilament proteins is increased (J:104770)

• treatment with allopurinol attenuates oxidation of myofilament proteins (J:104770)

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:104770 )

• mice show 3-fold higher xanthine oxidase activity and total xanthine oxidoreductase (combined xanthine oxidase and xanthine dehydrogenase) activities are higher in the myocardium

• oral treatment with allopurinol reduces xanthine oxidase/xanthine oxidoreductase activity to a level less than or comparable to controls

increased susceptibility to xenobiotic induced morbidity/mortality ( J:59433 )

• mice exhibit a higher incidence of sudden death with anesthesia

decreased physiological sensitivity to xenobiotic ( J:59433 )

• mice exhibit a blunted effect of adrenergic stimulation with isoproterenol on ventricular relaxation

mortality/aging

mortality/aging ( J:59433 )

N • unstressed mice are viable until at least 12 months of age without overt heart failure

increased susceptibility to xenobiotic induced morbidity/mortality ( J:59433 )

• mice exhibit a higher incidence of sudden death with anesthesia

muscle

abnormal myocardium layer morphology ( J:59433 )

• mice exhibit stunned myocardium

dilated cardiomyopathy ( J:104770 )

• 15% increase in left ventricular end-diastolic dimension, 32% increase in left ventricular end-systolic dimension, and a 15% decrease in fractional shortening

decreased cardiac muscle contractility ( J:59433 , J:104770 )

• systolic function is depressed as indicated by a decrease in the rate of pressure development (dP/dt max) and by reductions in the load-independent indices of preload-recruitable stroke work and end-systolic elastance (J:59433)

• 15% decrease in fractional shortening (J:104770)

• oral treatment with allopurinol at an early stage improves cardiac contractility (J:104770)

abnormal cardiac muscle relaxation ( J:59433 )

• diastolic relaxation is slowed

• mice exhibit a blunted effect of adrenergic stimulation with isoproterenol on ventricular relaxation

growth/size/body

enlarged heart ( J:59433 )

• cardiac enlargement

• however, heart walls are not atrophied and myocellular architecture is normal

increased heart weight ( J:59433 )

• modest increase in heart-to-body weight ratio

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:104770