Phenotypes associated with this allele

• Allele Symbol: Mybpc3^tm1Jse
• Allele Name: targeted mutation 1, Jonathan G Seidman
• Allele ID: MGI:2654419
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mybpc3^tm1Jse/Mybpc3^tm1Jse	involves: 129S/SvEv	MGI:3626358
hm2	Mybpc3^tm1Jse/Mybpc3^tm1Jse	Not Specified	MGI:2654421

Genotype
MGI:3626358

hm1

• Allelic Composition: Mybpc3^tm1Jse/Mybpc3^tm1Jse
• Genetic Background: involves: 129S/SvEv

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

cardiovascular system

increased heart weight ( J:98868 )

• at 10 to 20 weeks, increased heart/body weight ratios (5.2 0.4 mg/g vs wild-type 3.8 0.1 mg/g)

dilated heart left ventricle ( J:98868 )

• at 10 to 20 weeks, increased LV chamber end-diastolic dimensions

dilated cardiomyopathy ( J:98868 )

decreased cardiac stroke volume ( J:98868 )

• LV chamber dilation is associated with reduced stroke volume (loop width) and end-systolic elastance

abnormal cardiac muscle contractility ( J:98868 )

• at 10 to 20 weeks, significantly reduced ejection fraction (29 5 % vs wild-type 46 5 %); in addition, V3/V1 myosin ratio is significantly higher

• significantly shortened time course of mutant LV systolic stiffening (elastance), and peaks earlier (27.62.1 ms vs wild-type 47.81.6 ms)

• hearts reached 773% of peak elastance before ejection of peak

• earlier time-to-peak tension in intact RV trabeculae, increased unloaded shortening velocity (V_max) in skinned muscle strips, and markedly reduced myofilament stiffness and tension at diastolic calcium concentrations

increased cardiac muscle contractility ( J:98868 )

• under conditions of isometric contraction, intact RV trabeculae display earlier time-to-peak trabecular tension across various pacing rates, with significant slowing of tension decay rate

• absolute magnitude of systolic force development greater than that of wild-type trabeculae at slower rates

• absolute magnitude of systolic force development normal at physiological rates

abnormal cardiac muscle relaxation ( J:98868 )

• rate of pressure decline (-dP/dtmin) significantly reduced (-4842 224 mm Hg/s vs wild-type -9615 488 mm Hg/s)

• normal resting heart rates and a normal maximal rate of pressure rise (dP/dtmax)

muscle

dilated cardiomyopathy ( J:98868 )

abnormal cardiac muscle contractility ( J:98868 )

• at 10 to 20 weeks, significantly reduced ejection fraction (29 5 % vs wild-type 46 5 %); in addition, V3/V1 myosin ratio is significantly higher

• significantly shortened time course of mutant LV systolic stiffening (elastance), and peaks earlier (27.62.1 ms vs wild-type 47.81.6 ms)

• hearts reached 773% of peak elastance before ejection of peak

• earlier time-to-peak tension in intact RV trabeculae, increased unloaded shortening velocity (V_max) in skinned muscle strips, and markedly reduced myofilament stiffness and tension at diastolic calcium concentrations

increased cardiac muscle contractility ( J:98868 )

• under conditions of isometric contraction, intact RV trabeculae display earlier time-to-peak trabecular tension across various pacing rates, with significant slowing of tension decay rate

• absolute magnitude of systolic force development greater than that of wild-type trabeculae at slower rates

• absolute magnitude of systolic force development normal at physiological rates

abnormal cardiac muscle relaxation ( J:98868 )

• rate of pressure decline (-dP/dtmin) significantly reduced (-4842 224 mm Hg/s vs wild-type -9615 488 mm Hg/s)

• normal resting heart rates and a normal maximal rate of pressure rise (dP/dtmax)

growth/size/body

increased heart weight ( J:98868 )

• at 10 to 20 weeks, increased heart/body weight ratios (5.2 0.4 mg/g vs wild-type 3.8 0.1 mg/g)

Genotype
MGI:2654421

hm2

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

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 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 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