Phenotypes Associated with This Genotype

Genotype
MGI:3531468

• Allelic Composition: Myh6^tm1Jse/Myh6⁺
• Genetic Background: involves: 129X1/SvJ

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

behavior/neurological

abnormal locomotor activation ( J:32960 )

• reduced tolerance for vigorous exercise in swimming tests

cardiovascular system

abnormal heart morphology ( J:32960 )

• histological changes in heart tissue more consistent in males than females

abnormal myocardial fiber morphology ( J:32960 )

• hypertrophy of myocytes with large hyperchromatic nuclei by 30 weeks of age

myocardial fiber disarray ( J:32960 , J:95600 )

• myocardial fiber disarray becoming marked by 30 weeks of age (J:32960)

• slight myocyte disarray is noticeable in tissue from apex of mutant hearts at 10-20 weeks of age (J:95600)

abnormal heart atrium morphology ( J:32960 )

• some individuals with left atrial enlargement at 15 weeks of age, particularly among males

• left atrial enlargement more prevalent by 30 weeks of age, 100% of males and a third of females

cardiac fibrosis ( J:95600 )

• apexes of 2/4 mutant hearts have undergone slight but noticeable fibrosis and myocyte disarray compared to wild-type hearts

cardiac interstitial fibrosis ( J:32960 )

• moderate diffuse interstitial fibrosis by 30 weeks of age, starting as early as 15 weeks

• focal replacement granulation tissue at 30 weeks

decreased cardiac output ( J:32960 )

abnormal heart ventricle pressure ( J:32960 , J:47028 )

• discontinuous pressure change with ventricular relaxation (J:32960)

• end diastolic pressure reduced with increased Calcium concentration during heart perfusion although systolic pressure is normal (J:47028)

irregular heartbeat ( J:32960 , J:47028 )

• longer duration of relaxation (J:32960)

• maximal rate of relaxation reduced (J:47028)

abnormal myocardial fiber physiology ( J:95600 )

• mutants show marked differences in cross-bridge kinetics of isolated myosin and skinned strips of myocardium

• maximal velocity (V) of regulated thin filament (RTF) in an in vitro motility assay is increased by 8% in mutants vs wild-type

• myosin concentration at half-maximal V_RTF is reduced by 30% compared to wild-type

• characteristic frequency for oscillatory work production in skinned strips is 27% lower in mutants vs wild-type

• calcium sensitivity for isometric tension in skinned strips is comparable to wild-type

muscle

abnormal myocardial fiber morphology ( J:32960 )

• hypertrophy of myocytes with large hyperchromatic nuclei by 30 weeks of age

myocardial fiber disarray ( J:32960 , J:95600 )

• myocardial fiber disarray becoming marked by 30 weeks of age (J:32960)

• slight myocyte disarray is noticeable in tissue from apex of mutant hearts at 10-20 weeks of age (J:95600)

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:95600 )

• isolated myosin from 10-20 week-old mutant hearts shows a 38% increase in V_max of actin-activated ATP hydrolysis (ATPase) compared to wild-type

cellular

cardiac interstitial fibrosis ( J:32960 )

• moderate diffuse interstitial fibrosis by 30 weeks of age, starting as early as 15 weeks

• focal replacement granulation tissue at 30 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 14		DOID:0110320	OMIM:613251	J:32960 , J:95600