Phenotypes associated with this allele

• Allele Symbol: Myh6^tm3.1Jse
• Allele Name: targeted mutation 3.1, Jonathan G Seidman
• Allele ID: MGI:4837367
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Myh6^tm3.1Jse/Myh6^tm3.1Jse	involves: 129	MGI:6356706
ht2	Myh6^tm3.1Jse/Myh6^+	involves: 129	MGI:6356707
ht3	Myh6^tm3.1Jse/Myh6^+	involves: 129X1/SvJ	MGI:4837384

Genotype
MGI:6356706

hm1

• Allelic Composition: Myh6^tm3.1Jse/Myh6^tm3.1Jse
• Genetic Background: involves: 129

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

mortality/aging

postnatal lethality, complete penetrance ( J:247162 )

• 100% of mice die within 9 days after birth

cardiovascular system

myocardial fiber disarray ( J:247162 )

• myocyte disarray at 1 week of age

calcified myocardium ( J:247162 )

• hearts show areas in the myocardium with calcifications

increased heart atrium size ( J:247162 )

• atria are enlarged in 1 week old mice

cardiac hypertrophy ( J:247162 )

• heart ventricles show upregulation of hypertrophy markers shortly before death

• hearts show hypertrophy of all cardiac chambers at 1 week of age

increased cardiomyocyte apoptosis ( J:247162 )

• hearts show patches of dying myocardial cells

growth/size/body

cardiac hypertrophy ( J:247162 )

• heart ventricles show upregulation of hypertrophy markers shortly before death

• hearts show hypertrophy of all cardiac chambers at 1 week of age

cellular

increased cardiomyocyte apoptosis ( J:247162 )

• hearts show patches of dying myocardial cells

muscle

myocardial fiber disarray ( J:247162 )

• myocyte disarray at 1 week of age

calcified myocardium ( J:247162 )

• hearts show areas in the myocardium with calcifications

increased cardiomyocyte apoptosis ( J:247162 )

• hearts show patches of dying myocardial cells

Genotype
MGI:6356707

ht2

• Allelic Composition: Myh6^tm3.1Jse/Myh6⁺
• Genetic Background: involves: 129

cardiovascular system

myocardial fiber disarray ( J:247162 )

• myofiber disarray at 26 weeks of age

cardiac hypertrophy ( J:247162 )

• progressive concentric hypertrophy

thick ventricular wall ( J:247162 )

• left ventricular wall thickness is more than 20% greater than in wild-type mice at 26 weeks of age

cardiac interstitial fibrosis ( J:247162 )

• interstitial fibrosis at 26 weeks of age

increased cardiac muscle contractility ( J:247162 )

• % ejection fraction is increased

abnormal heart echocardiography feature ( J:247162 )

• echocardiography indicates increased left ventricular anterior wall thickness, left ventricular posterior wall thickness, and increased % ejection fraction

growth/size/body

cardiac hypertrophy ( J:247162 )

• progressive concentric hypertrophy

muscle

myocardial fiber disarray ( J:247162 )

• myofiber disarray at 26 weeks of age

increased cardiac muscle contractility ( J:247162 )

• % ejection fraction is increased

cellular

cardiac interstitial fibrosis ( J:247162 )

• interstitial fibrosis at 26 weeks of age

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

Genotype
MGI:4837384

ht3

• Allelic Composition: Myh6^tm3.1Jse/Myh6⁺
• Genetic Background: involves: 129X1/SvJ

cardiovascular system

heart left ventricle hypertrophy ( J:165269 )

• at 35 weeks but not prior to 20 weeks

thick ventricular wall ( J:165269 )

• cyclosporine A treatment accelerates development of increased left ventricular wall thickness (1.8-fold) unlike similarly treated wild-type mice

• mice treated with cyclosporine A and Tgf-beta neutralizing antibodies exhibit less maximal left ventricular wall thickness compared with mice treated with cyclosporine A and IgG

• mice treated with cyclosporin A and losartan exhibit less maximal left ventricular wall thickness compared with mice treated with only cyclosporin

• however, mice treated with cyclosporin A and losartan exhibit the same maximal left ventricular wall thickness as in similarly treated wild-type mice

cardiac fibrosis ( J:165269 )

• cyclosporine A treatment accelerates development of myocardial fibrosis (80-fold) unlike similarly treated wild-type mice

• mice treated with cyclosporine A and Tgf-beta neutralizing antibodies exhibit reduced cardiac fibrosis compared with mice treated with cyclosporine A and IgG

• mice treated with cyclosporin A and losartan exhibit 2.9-fold less fibrosis compared with mice treated with only cyclosporin A

abnormal cardiovascular system physiology ( J:165269 )

• non-myocyte cells from hypertrophic mice treated with cyclosporine A exhibit a 4-fold increase in proliferation compared with cells from similarly treated wild-type mice

• non-myocyte cells in regions with normal histological architecture from hypertrophic mice treated with cyclosporine A exhibit a 3.3-fold increase in proliferation compared with cells from similarly treated wild-type mice

• non-myocyte cells in left ventricular sections with focal fibrosis or overt interstitial expansion from hypertrophic mice treated with cyclosporine A exhibit a 4-fold increase in proliferation compared with cells from similarly treated wild-type mice

• proliferation of non-myocyte cells is greater in regions with focal fibrosis and expanded interstitium compared to in regions with normal architecture

• mice treated with cyclosporine A and Tgf-beta neutralizing antibodies exhibit reduced non-myocyte proliferation in regions with fibrosis and regions with preserved myocardial architecture compared with mice treated with cyclosporine A and IgG

• mice treated with cyclosporin A and losartan exhibit reduced non-myocyte cell proliferation in fibrotic regions (8-fold) and regions with preserved myocardial architecture compared with mice treated with mice treated with only cyclosporin A

• however, losartan treatment reduces proliferation in the hypertrophic hearts of mice treated with cyclosporin A to the level observed in similarly treated wild-type mice

cardiomyopathy ( J:165269 )

• mice exhibit hypertrophic cardiomyopathy at 35 weeks but not prior to 20 weeks

• cyclosporine A treatment accelerates development hypertrophic cardiomyopathy histopathology unlike similarly treated wild-type mice

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:165269 )

• cyclosporine A-treated mice accelerates increased left ventricular wall thickness (1.8-fold), overt hypertrophic cardiomyopathy histopathology, including myocardial fibrosis (80-fold), and preserved cardiac function unlike similarly treated wild-type mice

muscle

heart left ventricle hypertrophy ( J:165269 )

• at 35 weeks but not prior to 20 weeks

cardiomyopathy ( J:165269 )

• mice exhibit hypertrophic cardiomyopathy at 35 weeks but not prior to 20 weeks

• cyclosporine A treatment accelerates development hypertrophic cardiomyopathy histopathology unlike similarly treated wild-type mice

growth/size/body

heart left ventricle hypertrophy ( J:165269 )

• at 35 weeks but not prior to 20 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 14		DOID:0110320	OMIM:613251	J:165269