Mouse Genome Informatics
ht
    Myh6tm1Jse/Myh6+
involves: 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
behavior/neurological
• reduced tolerance for vigorous exercise in swimming tests

cardiovascular system
• histological changes in heart tissue more consistent in males than females
• 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
• hypertrophy of myocytes with large hyperchromatic nuclei 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)
• myocardial fiber disarray becoming marked by 30 weeks of age
• apexes of 2/4 mutant hearts have undergone slight but noticeable fibrosis and myocyte disarray compared to wild-type hearts
• moderate diffuse interstitial fibrosis by 30 weeks of age, starting as early as 15 weeks
• focal replacement granulation tissue at 30 weeks
• 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)
• longer duration of relaxation (J:32960)
• maximal rate of relaxation reduced (J:47028)
• 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 VRTF 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
• hypertrophy of myocytes with large hyperchromatic nuclei 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
• isolated myosin from 10-20 week-old mutant hearts shows a 38% increase in Vmax of actin-activated ATP hydrolysis (ATPase) compared to wild-type

Mouse Models of Human Disease
OMIM IDRef(s)
Cardiomyopathy, Familial Hypertrophic, 14; CMH14 613251 J:32960 , J:95600