Phenotypes Associated with This Genotype

Genotype
MGI:5912300

• Allelic Composition: Tg(Myh6-Tnni3*R193H)594Jmme/0
• Genetic Background: involves: C57BL/6 * SJL

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

behavior/neurological

impaired exercise endurance ( J:186721 )

• mice show a reduction in the number of running bouts per day

• however, the average distance run/day is not altered

cardiovascular system

small heart ( J:186721 )

decreased heart weight ( J:186721 )

• heart-to-body weight ratio is smaller in 6-7 month old mice

increased cardiac muscle contractility ( J:186721 )

• increase in circumferential shortening in 6-7 month old mice

decreased cardiac muscle relaxation ( J:186721 )

• reduction in left ventricle relaxation velocity and a decrease in the ratio of early left ventricle relaxation velocity to late left ventricle relaxation velocity during atrial contraction [EI(a)/AI(a)], indicating diastolic dysfunction

abnormal heart echocardiography feature ( J:186721 )

• 6-7 month old mice exhibit a smaller heart-to-body weight ratio, smaller left ventricular end diastolic chamber volume, and an increase in circumferential shortening

increased left ventricle diastolic pressure ( J:186721 )

• the E/EI(a) ratio, which correlates to pulmonary wedge pressures, is increased suggesting elevated left ventricular diastolic pressure

abnormal myocardial fiber physiology ( J:186721 )

• cardiac myocytes generate higher passive tensions across a range of sarcomere lengths without changes in intracellular caclium resulting in significant calcium independent cellular diastolic tone

• myocytes exhibit a biphasic response of relaxation to increased pacing frequency versus the negative staircase seen with calcium day

• calcium transient amplitude is blunted in myocytes despite normal mechanical shortening resulting in myocyte hypercontractility

increased systemic arterial diastolic blood pressure ( J:186721 )

• end diastolic pressure is elevated in 8-9 month old mice

cardiomyopathy ( J:186721 )

• hearts exhibit impaired relaxation and elevated end diastolic pressure indicative of restrictive cardiomyopathy

• however, no cardiac fibrosis, inflammation of myofibrillar disarray are seen at 6-7 months of age

homeostasis/metabolism

impaired exercise endurance ( J:186721 )

• mice show a reduction in the number of running bouts per day

• however, the average distance run/day is not altered

muscle

increased cardiac muscle contractility ( J:186721 )

• increase in circumferential shortening in 6-7 month old mice

decreased cardiac muscle relaxation ( J:186721 )

• reduction in left ventricle relaxation velocity and a decrease in the ratio of early left ventricle relaxation velocity to late left ventricle relaxation velocity during atrial contraction [EI(a)/AI(a)], indicating diastolic dysfunction

cardiomyopathy ( J:186721 )

• hearts exhibit impaired relaxation and elevated end diastolic pressure indicative of restrictive cardiomyopathy

• however, no cardiac fibrosis, inflammation of myofibrillar disarray are seen at 6-7 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
restrictive cardiomyopathy		DOID:397	OMIM:115210 OMIM:PS115210	J:186721