Phenotypes Associated with This Genotype

Genotype
MGI:2654421

• Allelic Composition: Mybpc3^tm1Jse/Mybpc3^tm1Jse
• Genetic Background: Not Specified

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

cardiovascular system

abnormal myocardial fiber morphology ( J:58295 )

• at 8-12 weeks, mutant hearts exhibit myocyte hypertrophy and myofibrillar disarray

myocardial fiber disarray ( J:58295 )

• at 8-12 weeks, mutant hearts display myofibrillar disarray

abnormal ventricle papillary muscle morphology ( J:58295 )

• 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

dilated heart left atrium ( J:58295 )

• 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)

enlarged heart ( J:58295 )

• homozygotes are fertile, produce normal litter sizes, and survive for >1 year but exhibit visibly enlarged hearts by 8-12 weeks of age

increased heart weight ( J:58295 )

• 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

abnormal heart left ventricle morphology ( J:58295 )

• at 8-12 weeks, homozygotes exhibit calcified plaques on the LV chamber walls

heart left ventricle hypertrophy ( J:58295 )

• 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

dilated heart left ventricle ( J:58295 )

• 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

thick ventricular wall ( J:58295 )

• by 8 weeks, homozygotes exhibit a significant increase in anterior and posterior LV wall thickness relative to wild-type mice

cardiac fibrosis ( J:58295 )

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

cardiac interstitial fibrosis ( J:58295 )

• at 8-12 weeks, 1 of 5 mutant hearts exhibit multifocal interstitial fibrosis

dilated cardiomyopathy ( J:58295 )

• neonatal homozygotes exhibit a progressive dilated cardiomyopathy associated with altered gene expression in cardiac tissue

dystrophic cardiac calcinosis ( J:58295 )

• 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

decreased heart left ventricle muscle contractility ( J:58295 )

• 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

growth/size/body

enlarged heart ( J:58295 )

• homozygotes are fertile, produce normal litter sizes, and survive for >1 year but exhibit visibly enlarged hearts by 8-12 weeks of age

heart left ventricle hypertrophy ( J:58295 )

• 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

increased heart weight ( J:58295 )

• 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

muscle

abnormal myocardial fiber morphology ( J:58295 )

• at 8-12 weeks, mutant hearts exhibit myocyte hypertrophy and myofibrillar disarray

myocardial fiber disarray ( J:58295 )

• at 8-12 weeks, mutant hearts display myofibrillar disarray

abnormal ventricle papillary muscle morphology ( J:58295 )

• 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

heart left ventricle hypertrophy ( J:58295 )

• 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

dilated cardiomyopathy ( J:58295 )

• neonatal homozygotes exhibit a progressive dilated cardiomyopathy associated with altered gene expression in cardiac tissue

decreased heart left ventricle muscle contractility ( J:58295 )

• 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

abnormal M line morphology ( J:58295 )

• 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

cellular

cardiac interstitial fibrosis ( J:58295 )

• at 8-12 weeks, 1 of 5 mutant hearts exhibit multifocal interstitial fibrosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 4		DOID:0110310	OMIM:115197	J:58295