Analysis Tools
mortality/aging
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• mice start to die by 8 weeks of age and 70-95% of mice die by 40 weeks; death is sudden with mice showing normal behavior within 24 hours of death
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cardiovascular system
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• heterogeneity in the size of ventricular myocytes, with some appearing hypertrophied and others appearing atrophied
• 20 week old ventricular myocytes exhibit sparse and misarranged myofibrils, discontinuous Z-bands, and deformed or completely disrupted mitochondria
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• hearts of 20 weeks, but not 8 weeks of age, are much larger than controls
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• left ventricle enlargement without increases in wall thickness in 20 week old hearts
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• interstitial fibrosis
• however, no inflammatory cell infiltrates are seen
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• heart to body weight ratio is 1.48-fold higher at 20 weeks of age, but is normal at 8 and 12 weeks of age
• ventricle shows increased expression of fetal-type ion channels carrying the hyperpolarization activated non-selective cation current and the T-type calcium current
• no lung or liver congestion is seen
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• mice show a progressive decline in fractional shortening and ejection fraction from 8 to 20 weeks of age
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• left ventricular end diastolic dimension and end systolic dimension are 30% and 80% higher at 20 weeks of age, but are normal at 8 weeks
• wall thickness is not affected, indicating progressive left ventricular dysfunction without left ventricle wall hypertrophy
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• mice show diminished systolic ventricular pressure and depression of both the maximal first derivative of the left ventricle pressure (dP/dtmax) and the maximal negative derivative of left ventricle pressure (dP/dtmin) at 20 weeks of age, but not at 8 weeks
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• mice that die suddenly during testing, show ventricular tachycardia and ventricular fibrillation followed by asystole
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• mice exhibit a variety of arrhythmias leading to sudden arrhythmic death
• 12 week old mice show increased susceptibility to ventricular arrhythmias induced by applied programmed electrical stimulation
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• mice that die suddenly during testing, show ventricular tachycardia and ventricular fibrillation followed by asystole
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• mice exhibit ventricular ectopies
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• mice exhibit second degree atrioventricular block and ventricular ectopies, including runs of ventricular tachycardia
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• PQ interval is longer
• however, no differences in heart rate, QRS time or QT interval are seen
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muscle
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• heterogeneity in the size of ventricular myocytes, with some appearing hypertrophied and others appearing atrophied
• 20 week old ventricular myocytes exhibit sparse and misarranged myofibrils, discontinuous Z-bands, and deformed or completely disrupted mitochondria
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• heart to body weight ratio is 1.48-fold higher at 20 weeks of age, but is normal at 8 and 12 weeks of age
• ventricle shows increased expression of fetal-type ion channels carrying the hyperpolarization activated non-selective cation current and the T-type calcium current
• no lung or liver congestion is seen
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• mice show a progressive decline in fractional shortening and ejection fraction from 8 to 20 weeks of age
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• left ventricular end diastolic dimension and end systolic dimension are 30% and 80% higher at 20 weeks of age, but are normal at 8 weeks
• wall thickness is not affected, indicating progressive left ventricular dysfunction without left ventricle wall hypertrophy
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• 20 week old ventricular myocytes exhibit discontinuous Z-bands
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growth/size/body
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• hearts of 20 weeks, but not 8 weeks of age, are much larger than controls
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cellular
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• interstitial fibrosis
• however, no inflammatory cell infiltrates are seen
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| dilated cardiomyopathy | DOID:12930 |
OMIM:PS115200 |
J:86837 | |
