Phenotypes associated with this allele

• Allele Symbol: Myh6^tm1.1Jpsc
• Allele Name: targeted mutation 1.1, Joachim P Schmitt
• Allele ID: MGI:6356699
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Myh6^tm1.1Jpsc/Myh6^tm1.1Jpsc	involves: 129	MGI:6356717
ht2	Myh6^tm1.1Jpsc/Myh6^+	involves: 129	MGI:6356708
ht3	Myh6^tm1.1Jpsc/Myh6^tm2Jse	involves: 129	MGI:6356709

Genotype
MGI:6356717

hm1

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

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

cardiovascular system

cardiovascular system phenotype ( J:247162 )

N • morphology and function of hearts do not differ from controls and mice do not show cardiac hypertrophy

Genotype
MGI:6356708

ht2

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

cardiovascular system

cardiovascular system phenotype ( J:247162 )

N • end-diastolic left ventricular anterior wall thickness and dimensions, as well as fractional shortening are normal at 26 weeks of age and 8 week old mice show normal left ventricular pressures, contraction and relaxation

N • hearts show no detectable morphological differences at 78 weeks of age

cardiac hypertrophy ( J:247162 )

• treatment with cyclosporine exacerbates the hypertrophic response, with mice developing symmetrical left ventricular wall thickening after 3 weeks of treatment

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:247162 )

• treatment with cyclosporine exacerbates the hypertrophic response, with mice developing symmetrical left ventricular wall thickening after 3 weeks of treatment

growth/size/body

cardiac hypertrophy ( J:247162 )

• treatment with cyclosporine exacerbates the hypertrophic response, with mice developing symmetrical left ventricular wall thickening after 3 weeks of treatment

Genotype
MGI:6356709

ht3

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

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 heart ventricle 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 heart ventricle 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