Phenotypes Associated with This Genotype

Genotype
MGI:5908460

• Allelic Composition: Tg(Myh6-Mybpc3*)32Rbns/0
• Genetic Background: Not Specified

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

cardiovascular system

abnormal heart morphology ( J:127656 )

• 13 month old adults exhibit increased levels of the following cytoskeleton components: intermediate filament protein, desmin, and alpha-B-crystallin, in hearts

abnormal myocardial fiber morphology ( J:50237 )

• individual myocytes exhibit oval-shaped foci

• myofibrils show signs of disorganization with T-tubules slightly distended and some mitochondria showing abnormal morphology

myocardial fiber degeneration ( J:50237 )

• scattered degenerating myocytes, adjacent to normal cells, are seen throughout the chambers of the heart

• ventricular myocytes in late stages of dysgenesis show some profiles of sarcoplasmic reticulum, lipid droplets, and a rim of myofibrils along the sarcolemma in degenerated parts of the cell

• however, mice show no cardiac hypertrophy or dilation at 25 weeks of age and no differences in heart contraction, relaxation, or responses to increased workload, or morbidity or mortality

increased heart weight ( J:127656 )

• heart weight/body weight ratios are increased about 17% compared to controls

cardiac hypertrophy ( J:127656 )

• mild cardiac hypertrophy develops in older mice (about 14 months of age)

decreased heart rate ( J:127656 )

• mice exhibit a slower heart rate during exercise sessions, with about 50% of mice showing a precipitous drop in heart rate

• mice subjected to beta-adrenergic stimulation via subcutaneous isoproterenol administration exhibit decreased heart rates after the third day of the trial

• however, no cardiac hypertrophy results from exercise

sinus bradycardia ( J:127656 )

• the 2 of 12 mice administered isoproterenol that die showed sinus bradycardia

abnormal myocardial fiber physiology ( J:50237 )

• isolated ventricular fibers show increased calcium sensitivity to force development and decreased maximum relative power

increased response of heart to induced stress ( J:127656 )

• mice subjected to treadmill exercise exhibit a decrease in exercise capacity with slower heart rate and death during or after exercise trail in 50% of mice

• mice treated with isoproterenol to induce beta-adrenergic stimulation exhibit reduced heart rates and a low level of death

behavior/neurological

impaired exercise endurance ( J:127656 )

• 4 of 8 mice subjected to sub-maximal treadmill exercise die during or immediately after the exercise trial

• mice show decrease in exercise capacity as evidenced by decreased exercise duration and increased bar touches

• mice older than 1 year of age fail to maintain even modest levels of performance on the treadmill

muscle

abnormal myocardial fiber morphology ( J:50237 )

• individual myocytes exhibit oval-shaped foci

• myofibrils show signs of disorganization with T-tubules slightly distended and some mitochondria showing abnormal morphology

myocardial fiber degeneration ( J:50237 )

• scattered degenerating myocytes, adjacent to normal cells, are seen throughout the chambers of the heart

• ventricular myocytes in late stages of dysgenesis show some profiles of sarcoplasmic reticulum, lipid droplets, and a rim of myofibrils along the sarcolemma in degenerated parts of the cell

• however, mice show no cardiac hypertrophy or dilation at 25 weeks of age and no differences in heart contraction, relaxation, or responses to increased workload, or morbidity or mortality

abnormal sarcomere morphology ( J:50237 )

• ventricular myocytes in the early degenerative stages show a lack of sarcomeric organization in only small areas adjacent to the nucleus

homeostasis/metabolism

impaired exercise endurance ( J:127656 )

• 4 of 8 mice subjected to sub-maximal treadmill exercise die during or immediately after the exercise trial

• mice show decrease in exercise capacity as evidenced by decreased exercise duration and increased bar touches

• mice older than 1 year of age fail to maintain even modest levels of performance on the treadmill

increased response of heart to induced stress ( J:127656 )

• mice subjected to treadmill exercise exhibit a decrease in exercise capacity with slower heart rate and death during or after exercise trail in 50% of mice

• mice treated with isoproterenol to induce beta-adrenergic stimulation exhibit reduced heart rates and a low level of death

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:127656 )

• 4 of 8 mice subjected to sub-maximal treadmill exercise die during or immediately after the exercise trial

• 2 of 12 mice administered isoproterenol die in early stages, between the third and fourth days

growth/size/body

increased heart weight ( J:127656 )

• heart weight/body weight ratios are increased about 17% compared to controls

cardiac hypertrophy ( J:127656 )

• mild cardiac hypertrophy develops in older mice (about 14 months of age)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 4		DOID:0110310	OMIM:115197	J:50237 , J:127656