Analysis Tools
growth/size/body
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• increase in heart weight and heart weight-to-body weight ratio at P19
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mortality/aging
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• mice die 15-33 days after birth with a median survival of 20 days
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• mice die 15-33 days after birth with a median survival of 20 days
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cardiovascular system
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• at P19, isolated cardiomyocytes are 37% longer on average than wild-type cardiomyocytes, with no change in width
• late-stage hearts display general myofibril disarray showing myofibril misalignment, broad Z-discs, T-tubule and sarcoplasmic reticulum dilation, mislocalization and increased convolutions of intercalated discs, and mitochondrial abnormalities including swelling and loss of cristae with intact outer double membranes
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• myofibrils in late-stage hearts show mislocalization and increased convolutions of intercalated discs
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• hearts show shorter thin filaments as early as E12.5, with up to 15% reduction in length at P15
• neonatal cardiomyocytes from P1-P2 mice cultured for 5-6 days have shorter thin filaments
• however, thin filament lengths are unchanged in the extensor digitorum longus and soleus muscles
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• increase in heart weight and heart weight-to-body weight ratio at P19
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• hearts show enlarged ventricular lumens at P15
• however, increase in fibrosis is not seen
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• thin ventricular walls at P6 and P15
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• thickness of the left ventricle walls at end diastole is reduced
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• hearts are dilated by P15
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• internal diameter of the left ventricle is larger
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• mice present with rapid progression of dilated cardiomyopathy; thinner left ventricle walls and reduced ejection fraction with no change in chamber dimension is seen at P6, by P15 hearts are dilated, and by P19, about 50% of mice die from cardiac failure, with increase in heart weight and expression of heart failure markers
• ratio of wall thickness to chamber diameter is decreased, consistent with eccentric remodeling
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• the ejection fraction is reduced by nearly 60% at P15
• neonatal cardiomyocytes exhibit a ~20% reduction in contractile force
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cellular
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• fewer mitochondria in hearts at P20
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muscle
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• at P19, isolated cardiomyocytes are 37% longer on average than wild-type cardiomyocytes, with no change in width
• late-stage hearts display general myofibril disarray showing myofibril misalignment, broad Z-discs, T-tubule and sarcoplasmic reticulum dilation, mislocalization and increased convolutions of intercalated discs, and mitochondrial abnormalities including swelling and loss of cristae with intact outer double membranes
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• myofibrils in late-stage hearts show mislocalization and increased convolutions of intercalated discs
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• mice present with rapid progression of dilated cardiomyopathy; thinner left ventricle walls and reduced ejection fraction with no change in chamber dimension is seen at P6, by P15 hearts are dilated, and by P19, about 50% of mice die from cardiac failure, with increase in heart weight and expression of heart failure markers
• ratio of wall thickness to chamber diameter is decreased, consistent with eccentric remodeling
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• the ejection fraction is reduced by nearly 60% at P15
• neonatal cardiomyocytes exhibit a ~20% reduction in contractile force
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• isolated cardiomyocytes exhibit reduced sarcomere lengths
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• broader Z-disks in hearts at P6 but not at P1
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