Mouse Genome Informatics
hm
    Mybpc3tm1Jse/Mybpc3tm1Jse
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
cardiovascular system
• by 8-12 weeks, homozygotes exhibit a significantly increased left atrium diameter relative to wild-type mice (1.77 0.13 mm vs 1.53 0.08 mm, respectively)
• at 8-12 weeks, mutant hearts exhibit myocyte hypertrophy and myofibrillar disarray
• at 8 weeks, 10 of 10 homozygotes display calcification of the papillary muscles and focal lesions within the LV; in 6 mutants these changes are moderate to severe
• at 8-12 weeks, mutant hearts display myofibrillar disarray
• homozygotes are fertile, produce normal litter sizes, and survive for >1 year but exhibit visibly enlarged hearts by 8-12 weeks of age
• at 8-12 weeks, homozygotes display significantly increased total heart weights relative to wild-type mice (177.0 5.7 mg vs 113.8 3.8 mg, respectively); heart-to-body weights are also significantly increased
• at 8-12 weeks, homozygotes exhibit calcified plaques on the LV chamber walls
• at 8-12 weeks, homozygotes display significantly increased LV weights relative to wild-type mice (136.0 7.5 mg vs. 80.0 4.8 mg, respectively)
• LV-to-body weight ratios are also significantly increased whereas RV and left and right atria are of normal size and weights
• at birth (P0-P3) and throughout adulthood (>3 weeks), mutant hearts display left ventricular dilation with increased LV diastolic and systolic diameters relative to wild-type hearts; myocardial hypertrophy increases as mice mature
• by 8 weeks, homozygotes exhibit a significant increase in anterior and posterior LV wall thickness relative to wild-type mice
• at 8-12 weeks, 1 of 5 mutant hearts exhibit slight perivascular fibrosis in subendocardial papillary muscle
• at 8-12 weeks, 1 of 5 mutant hearts exhibit multifocal interstitial fibrosis
• neonatal homozygotes exhibit a progressive dilated cardiomyopathy associated with altered gene expression in cardiac tissue
• at 8-12 weeks, 3 of 5 mutant hearts show dystrophic calcification of variable extent and location
• focal LV and RV calcifications and multifocal intramural calcification are noted in 2 of 5 mutant hearts; subendocardial calcification with multifocal interstitial fibrosis is noted in 1 of 5 mutant hearts
• at birth (P0-P3) and throughout adulthood (>3 weeks), mutant hearts display reduced LV fractional shortening relative to wild-type hearts
• adult homozygotes show depressed systolic contractility with diastolic dysfunction: dP/dTmin, dP/dTratio, end-diastolic volume, time to peak filling, relaxation time (tau), and chamber compliance (normalized beta) are all abnormal

muscle
• at 8-12 weeks, mutant hearts exhibit myocyte hypertrophy and myofibrillar disarray
• neonatal homozygotes exhibit a progressive dilated cardiomyopathy associated with altered gene expression in cardiac tissue
• at birth (P0-P3) and throughout adulthood (>3 weeks), mutant hearts display reduced LV fractional shortening relative to wild-type hearts
• adult homozygotes show depressed systolic contractility with diastolic dysfunction: dP/dTmin, dP/dTratio, end-diastolic volume, time to peak filling, relaxation time (tau), and chamber compliance (normalized beta) are all abnormal
• at 12 weeks, mutant hearts display well-organized sarcomeres with regularly aligned A-bands, I-bands, and Z-lines; however, M-lines are frequently absent in sarcomeres from the LV whereas sarcomeres derived from the RV display well-defined M-lines

homeostasis/metabolism
• at 8-12 weeks, 1 of 5 mutant hearts exhibit slight perivascular fibrosis in subendocardial papillary muscle
• at 8-12 weeks, 1 of 5 mutant hearts exhibit multifocal interstitial fibrosis

Mouse Models of Human Disease
OMIM IDRef(s)
Cardiomyopathy, Familial Hypertrophic, 4; CMH4 115197 J:58295