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Phenotypes Associated with This Genotype
Genotype
MGI:5904828
Allelic
Composition
Tg(Myh6-CACNA1C)M1Aschw/0
Genetic
Background
involves: FVB/N
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See publication links below for author information.
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice begin to die at 8-10 months of age from heart failure, with very few surviving more than 1 year

growth/size/body
• severe cardiomegaly in all 4 cardiac chambers by 8 months of age
• heart-to-body weight differences are increased, indicating a mild hypertrophy without ventricular dysfunction

cardiovascular system
• calcium-laden cells occur at a low frequency in 8 month old hearts
• average cell capacitance is larger in ventricular cardiomyocytes, indicating cellular hypertrophy (J:129494)
• cardiomyocytes from 2, 4, and 8 month old mice show an increase in calcium channel density (J:134761)
• mild thickening at 8 months of age
• severe cardiomegaly in all 4 cardiac chambers by 8 months of age
• heart-to-body weight differences are increased, indicating a mild hypertrophy without ventricular dysfunction
• left ventricular mass is increased 23%
• left ventricular end-diastolic dimension is minimally increased
• minimal increase in left ventricular posterior wall thickness
• extensive interstitial fibrosis separates groups of myocytes in ventricles
• fibrosis and repair are present in 2 and 4 month old hearts
• hypertrophic myopathy (4-chamber dilation with mild thickening of the interventricular septum) in 8 month old hearts
• basal heart contractility and relaxation are higher than in controls
• hearts in ex vivo show increased basal contractility
• however, no differences are seen in left ventricular end-systolic dimension, septal wall thickness, or fractional shortening percentage
• basal heart relaxation is higher than in controls
• 8 month old, but not 2 or 4 month old, hearts show presence of apoptosis
• L-type voltage-dependent calcium channel current amplitude is larger in ventricular myocytes indicating increased calcium current
• isolated ventricular myocytes stimulated with isoproterenol or forskolin show lower increases in peak calcium channel currents compared to controls
• however, when the current amplitude is normalized for cell capacitance, there is no difference between transgenic and nontransgenic cardiomyocytes
• no differences are seen in the voltage dependence of activation or the activation/inactivation kinetics of the channels
• mice begin to show signs of heart failure beginning at 8 months of age, showing lethargic movement, labored breathing, ruffled fur, hunched posture, peripheral edema, ascites, hepatomegaly and edematous lungs

cellular
• 8 month old, but not 2 or 4 month old, hearts show presence of apoptosis

homeostasis/metabolism
• white gelatinous zones are seen in the atria by 8 months of age, suggesting organized thrombi
• mice exhibit peripheral edema at heart failure
• edematous lungs are seen at heart failure
• ascites is seen at heart failure
• infusion of the beta-adrenergic receptor agonist, isoproterenol, does not elicit the expected inotropic and lusitropic (relaxation, diastole) increases seen in controls
• the increase in contractility induced by forskolin is decreased in mutant hearts compared to controls
• isoproterenol-stimulated adenylyl cyclase activity is absent in membranes of cardiomyocytes

muscle
• average cell capacitance is larger in ventricular cardiomyocytes, indicating cellular hypertrophy (J:129494)
• cardiomyocytes from 2, 4, and 8 month old mice show an increase in calcium channel density (J:134761)
• hypertrophic myopathy (4-chamber dilation with mild thickening of the interventricular septum) in 8 month old hearts
• basal heart contractility and relaxation are higher than in controls
• hearts in ex vivo show increased basal contractility
• however, no differences are seen in left ventricular end-systolic dimension, septal wall thickness, or fractional shortening percentage
• basal heart relaxation is higher than in controls
• 8 month old, but not 2 or 4 month old, hearts show presence of apoptosis

respiratory system
• edematous lungs are seen at heart failure

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
congestive heart failure DOID:6000 J:134761
hypertrophic cardiomyopathy DOID:11984 J:134761


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
01/24/2023
MGI 6.22
The Jackson Laboratory