Phenotypes Associated with This Genotype

Genotype
MGI:6356709

• Allelic Composition: Myh6^tm1.1Jpsc/Myh6^tm2Jse
• Genetic Background: involves: 129

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

mortality/aging

premature death ( J:247162 )

• mice live to adulthood but die prematurely at a mean age of 62 +/- 8 weeks

cardiovascular system

increased myocardial fiber size ( J:247162 )

• heart myocytes are enlarged

increased heart weight ( J:247162 )

• heart-to-body weight ratio is increased compared to wild-type mice or Myh6^tm1.1Jpsc heterozygotes

cardiac hypertrophy ( J:247162 )

• hypertrophy of hearts rapidly progresses and exceeds the wall thickness of Myh6^tm1.1Jpsc heterozygotes by more than 50% at 26 weeks of age

• markers of hypertrophy are elevated already at 6-8 weeks of age

myocardium hypertrophy ( J:247162 )

thick ventricular wall ( J:247162 )

• left ventricular wall thickness is almost doubled compared to Myh6^tm1.1Jpsc heterozygotes

cardiac fibrosis ( J:247162 )

• myocardium shows massive fibrosis that is detectable at 10 weeks of age and progresses over time

abnormal cardiovascular system physiology ( J:247162 )

• left atrial tissue generates only 46% of the force produced by Myh6^tm1.1Jpsc heterozygous tissue and the speed of force generation and speed of force decay are reduced

• beta-adrenergic stimulation fails to enhance slow contraction and relaxation of hearts indicating a loss of cardiac reserve

decreased cardiac stroke volume ( J:247162 )

• ventricular stroke volume is depressed in 26 week old mice

decreased cardiac muscle contractility ( J:247162 )

• end-diastolic volumes are low and ventricular stroke volume is depressed in 26 week old mice and left ventricles show depressed velocities of pressure rise and low maximal left ventricular pressures at 6-8 weeks of age, indicating impaired systolic function

• however, fractional shortening is conserved at 26 weeks of age

abnormal cardiac muscle relaxation ( J:247162 )

• left ventricular relaxation is impaired in 6-8 week old mice, with reduced left ventricular end-diastolic volume and reduced maximum speed of pressure decay, indicating diastolic dysfunction before the development of hypertrophy and fibrosis

abnormal heart echocardiography feature ( J:247162 )

• echocardiography indicates increased left ventricular anterior wall thickness and posterior wall thickness in systole and in diastole, decreased left ventricle diameter, and decreased stroke volume

muscle

increased myocardial fiber size ( J:247162 )

• heart myocytes are enlarged

myocardium hypertrophy ( J:247162 )

decreased cardiac muscle contractility ( J:247162 )

• end-diastolic volumes are low and ventricular stroke volume is depressed in 26 week old mice and left ventricles show depressed velocities of pressure rise and low maximal left ventricular pressures at 6-8 weeks of age, indicating impaired systolic function

• however, fractional shortening is conserved at 26 weeks of age

abnormal cardiac muscle relaxation ( J:247162 )

• left ventricular relaxation is impaired in 6-8 week old mice, with reduced left ventricular end-diastolic volume and reduced maximum speed of pressure decay, indicating diastolic dysfunction before the development of hypertrophy and fibrosis

growth/size/body

increased heart weight ( J:247162 )

• heart-to-body weight ratio is increased compared to wild-type mice or Myh6^tm1.1Jpsc heterozygotes

cardiac hypertrophy ( J:247162 )

• hypertrophy of hearts rapidly progresses and exceeds the wall thickness of Myh6^tm1.1Jpsc heterozygotes by more than 50% at 26 weeks of age

• markers of hypertrophy are elevated already at 6-8 weeks of age

myocardium hypertrophy ( J:247162 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 14		DOID:0110320	OMIM:613251	J:247162