Phenotypes associated with this allele

• Allele Symbol: Myocd^tm1Msp
• Allele Name: targeted mutation 1, Michael S Parmacek
• Allele ID: MGI:3773717
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Myocd^tm1Msp/Myocd^tm1Msp	involves: 129	MGI:5907043
cn2	Myocd^tm1Msp/Myocd^tm1Msp H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129/Sv * C57BL/6 * CBA	MGI:3797650
cn3	Myocd^tm1Msp/Myocd^tm1Msp A1cf^Tg(Myh6-cre/Esr1*)1Jmk/A1cf^+	involves: 129/Sv * C57BL/6J * FVB/N	MGI:5907042
cn4	Myocd^tm1Msp/Myocd^tm1Msp Tg(Pax3-cre)1Joe/0	involves: 129/Sv * C57BL/6 * SJL	MGI:3797716
cn5	Myocd^tm1Msp/Myocd^tm1Msp Tg(Myh6-cre)2182Mds/0	involves: 129/Sv * FVB/N	MGI:5907041

Genotype
MGI:5907043

cn1

• Allelic Composition: Myocd^tm1Msp/Myocd^tm1Msp
• Genetic Background: involves: 129

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

cardiovascular system

abnormal myocardial fiber morphology ( J:154666 )

• neonatal primary cardiomyocytes transduced with an adenovirus expressing cre recombinase (Ad-cre) show loss of the loosely arranged myofibrils within 72 hours of Ad-cre infection

cellular

increased cardiomyocyte apoptosis ( J:154666 )

• cardiomyocytes infected with Ad-cre show widespread apoptosis

muscle

abnormal myocardial fiber morphology ( J:154666 )

• neonatal primary cardiomyocytes transduced with an adenovirus expressing cre recombinase (Ad-cre) show loss of the loosely arranged myofibrils within 72 hours of Ad-cre infection

increased cardiomyocyte apoptosis ( J:154666 )

• cardiomyocytes infected with Ad-cre show widespread apoptosis

Genotype
MGI:3797650

cn2

• Allelic Composition: Myocd^tm1Msp/Myocd^tm1Msp; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

mortality/aging

postnatal lethality, complete penetrance ( J:131288 )

• majority of mutants die before P3

cardiovascular system

abnormal angiogenesis ( J:131288 )

• the architecture of the neointima and tunica media of the ductus arteriosus is disturbed

• increase in fibronectin and laminin in the ductus arteriosus

patent ductus arteriosus ( J:131288 )

• all mutants at P2 exhibit patent ductus arteriosus

• E16.5 mutants exhibit diminished expression of smooth muscle cell contractile proteins in the ductus arteriosus

• however, patterning of the cardiac outflow tract and great arteries is normal

abnormal vascular smooth muscle morphology ( J:131288 )

• the smooth muscle cells of the ductus arteriosus are heterogeneous in size with a loss of spindle-like cell morphology

• the smooth muscle cells of the ductus arteriosus have relatively few myofibers and show an increase in synthetic organelles, including the rough ER and Golgi

homeostasis/metabolism

cyanosis ( J:131288 )

• pups become cyanotic shortly after birth

muscle

abnormal vascular smooth muscle morphology ( J:131288 )

• the smooth muscle cells of the ductus arteriosus are heterogeneous in size with a loss of spindle-like cell morphology

• the smooth muscle cells of the ductus arteriosus have relatively few myofibers and show an increase in synthetic organelles, including the rough ER and Golgi

cellular

patent ductus arteriosus ( J:131288 )

• all mutants at P2 exhibit patent ductus arteriosus

• E16.5 mutants exhibit diminished expression of smooth muscle cell contractile proteins in the ductus arteriosus

• however, patterning of the cardiac outflow tract and great arteries is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
patent ductus arteriosus		DOID:13832	OMIM:607411	J:131288

Genotype
MGI:5907042

cn3

• Allelic Composition: Myocd^tm1Msp/Myocd^tm1Msp; A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
• Genetic Background: involves: 129/Sv * C57BL/6J * FVB/N

mortality/aging

premature death ( J:154666 )

• 4 month old mice treated with tamoxifen become lethargic within 3-4 days of tamoxifen exposure and die within 7 days

cardiovascular system

abnormal myocardial fiber morphology ( J:154666 )

• derangements in cardiomyocyte structure and myofibrillar organization are seen throughout the hearts of tamoxifen-treated adult mice

• cardiomyocytes of tamoxifen-treated adult mice exhibit indistinct desmosomes and adherens junctions

abnormal intercalated disk morphology ( J:154666 )

• structure of the intercalated disc is disrupted in the hearts of tamoxifen-treated adult mice

abnormal myocardial fiber myofibril morphology ( J:154666 )

• myofibrillar striations are absent in tamoxifen-treated hearts

myocardial fiber degeneration ( J:154666 )

• loss of cardiomyocytes in tamoxifen-treated adults

myocardial fiber disarray ( J:154666 )

• cardiomyocyte disarray with myocyte loss in hearts of tamoxifen-treated adult mice

• sparse, randomly oriented myofibers are seen throughout the sarcoplasm of hearts of tamoxifen-treated adult mice

enlarged heart ( J:154666 )

• hearts of tamoxifen-treated adult mice are enlarged

pericardial effusion ( J:154666 )

• hearts of tamoxifen-treated adult mice show large pericardial effusions

cardiac fibrosis ( J:154666 )

• fibrosis in hearts of tamoxifen-treated adult mice

dilated cardiomyopathy ( J:154666 )

• 6 days after tamoxifen treatment, adult mice exhibit severe dilated cardiomyopathy involving all 4 chambers

decreased cardiac muscle contractility ( J:154666 )

• mean ejection fraction is decreased in tamoxifen-treated adult mice

growth/size/body

enlarged heart ( J:154666 )

• hearts of tamoxifen-treated adult mice are enlarged

cellular

abnormal myocardial fiber myofibril morphology ( J:154666 )

• myofibrillar striations are absent in tamoxifen-treated hearts

increased cardiomyocyte apoptosis ( J:154666 )

• widespread cardiomyocyte apoptosis in tamoxifen-treated adult mice

homeostasis/metabolism

pericardial effusion ( J:154666 )

• hearts of tamoxifen-treated adult mice show large pericardial effusions

muscle

abnormal myocardial fiber morphology ( J:154666 )

• derangements in cardiomyocyte structure and myofibrillar organization are seen throughout the hearts of tamoxifen-treated adult mice

• cardiomyocytes of tamoxifen-treated adult mice exhibit indistinct desmosomes and adherens junctions

abnormal intercalated disk morphology ( J:154666 )

• structure of the intercalated disc is disrupted in the hearts of tamoxifen-treated adult mice

abnormal myocardial fiber myofibril morphology ( J:154666 )

• myofibrillar striations are absent in tamoxifen-treated hearts

myocardial fiber degeneration ( J:154666 )

• loss of cardiomyocytes in tamoxifen-treated adults

myocardial fiber disarray ( J:154666 )

• cardiomyocyte disarray with myocyte loss in hearts of tamoxifen-treated adult mice

• sparse, randomly oriented myofibers are seen throughout the sarcoplasm of hearts of tamoxifen-treated adult mice

dilated cardiomyopathy ( J:154666 )

• 6 days after tamoxifen treatment, adult mice exhibit severe dilated cardiomyopathy involving all 4 chambers

decreased cardiac muscle contractility ( J:154666 )

• mean ejection fraction is decreased in tamoxifen-treated adult mice

increased cardiomyocyte apoptosis ( J:154666 )

• widespread cardiomyocyte apoptosis in tamoxifen-treated adult mice

abnormal sarcomere morphology ( J:154666 )

• loss of sarcomeres in the hearts of tamoxifen-treated adult mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:154666

Genotype
MGI:3797716

cn4

• Allelic Composition: Myocd^tm1Msp/Myocd^tm1Msp; Tg(Pax3-cre)1Joe/0
• Genetic Background: involves: 129/Sv * C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:131288 )

• die before P3

cardiovascular system

patent ductus arteriosus ( J:131288 )

• all mutants at P2 exhibit patent ductus arteriosus

• E16.5 mutants exhibit diminished expression of smooth muscle cell contractile proteins in the ductus arteriosus

• however, patterning of the cardiac outflow tract and great arteries is normal

cellular

patent ductus arteriosus ( J:131288 )

• all mutants at P2 exhibit patent ductus arteriosus

• E16.5 mutants exhibit diminished expression of smooth muscle cell contractile proteins in the ductus arteriosus

• however, patterning of the cardiac outflow tract and great arteries is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
patent ductus arteriosus		DOID:13832	OMIM:607411	J:131288

Genotype
MGI:5907041

cn5

• Allelic Composition: Myocd^tm1Msp/Myocd^tm1Msp; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129/Sv * FVB/N

mortality/aging

premature death ( J:154666 )

• 90% of mice die by 10 months of age and no mice survive beyond 1 year of age

postnatal lethality, incomplete penetrance ( J:154666 )

• about 20% of mice die before 3 weeks of age

cellular

abnormal myocardial fiber myofibril morphology ( J:154666 )

• extensive loss of myofibrillar striations

cardiovascular system

abnormal intercalated disk morphology ( J:154666 )

• intercalated discs of hearts appear abnormal

• serpiginous intercalated discs with indistinct desmosomes and adherens junctions

abnormal myocardial fiber myofibril morphology ( J:154666 )

• extensive loss of myofibrillar striations

myocardial fiber degeneration ( J:154666 )

• hearts show extensive loss of cardiomyocytes

increased heart atrium size ( J:154666 )

• both the left and right atrium are enlarged in 10 month old mice

enlarged heart ( J:154666 )

• four-chamber enlargement in 10 month old mice

increased heart ventricle size ( J:154666 )

• both the left and right ventricles are enlarged in 10 month old mice

pericardial effusion ( J:154666 )

cardiac fibrosis ( J:154666 )

• 11.2% of the left ventricle myocardium shows fibrosis compared to 0.46% in controls

dilated cardiomyopathy ( J:154666 )

• mice develop lethal dilated cardiomyopathy

decreased cardiac muscle contractility ( J:154666 )

• systolic function is depressed

• mean ejection fraction is reduced (24.5% vs 57.8% in controls)

abnormal heart echocardiography feature ( J:154666 )

• echocardiography shows enlargement of the left atrium, left ventricle, right atrium, and right ventricle in 10 month old hearts

homeostasis/metabolism

pericardial effusion ( J:154666 )

abnormal cardiac thrombosis ( J:154666 )

• atrial and ventricular thromboses are seen in 10 month old hearts

abnormal atrial thrombosis ( J:154666 )

• atrial thromboses are seen in 10 month old hearts

muscle

abnormal intercalated disk morphology ( J:154666 )

• intercalated discs of hearts appear abnormal

• serpiginous intercalated discs with indistinct desmosomes and adherens junctions

abnormal myocardial fiber myofibril morphology ( J:154666 )

• extensive loss of myofibrillar striations

myocardial fiber degeneration ( J:154666 )

• hearts show extensive loss of cardiomyocytes

dilated cardiomyopathy ( J:154666 )

• mice develop lethal dilated cardiomyopathy

decreased cardiac muscle contractility ( J:154666 )

• systolic function is depressed

• mean ejection fraction is reduced (24.5% vs 57.8% in controls)

abnormal sarcomere morphology ( J:154666 )

• shortened, hypercontracted sarcomeres in hearts

growth/size/body

enlarged heart ( J:154666 )

• four-chamber enlargement in 10 month old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:154666