cardiovascular system
• extensive biventricular epicardial and endocardial fibrosis
• exercised mice show extensive biventricular fibrosis
• mice treated daily with the GSK3B inhibitor SB216763 at 3 weeks of age do not exhibit biventricular epicardial and endocardial fibrosis
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• mice show reduced ejection fraction and fractional shortening by 8 weeks of age
• exercised mice show reduced ejection fraction and fractional shortening compared to exercised wild-type mice
• SB216763 treatment improves cardiac function
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• echocardiography shows reduced interventricular septal end-systolic volume, increased left ventricular internal diameter end-diastolic volume and end-systolic volume, decreased left ventricular posterior wall end systole, and reduced fractional shortening and ejection fraction
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• mice show increased ventricular ectopy
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• prolongation of the average QRS duration
• exercised mice show longer mean QRS complex duration than exercised wild-type mice
• SB216763 treatment normalizes QRS duration
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• mice show reduced S wave amplitude
• exercised mice show reduced S wave amplitude
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• mice develop cardiomyopathy by 8 weeks of age
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• biventricular and endocardial inflammation
• exercised mice show extensive biventricular fibrosis and inflammation
• mice treated daily with SB216763 at 3 weeks of age do not exhibit biventricular epicardial and endocardial fibrosis inflammation
|
mortality/aging
• 55% of mice die while swimming, with mean time of exercise at death of 7.8 +/- 0.6 weeks
• SB216763 treatment improves survival of exercised mice
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immune system
• mice treated daily with SB216763 at 3 weeks of age do not exhibit biventricular epicardial and endocardial fibrosis inflammation
• biventricular and endocardial inflammation
• exercised mice show extensive biventricular fibrosis and inflammation
|
muscle
• mice show reduced ejection fraction and fractional shortening by 8 weeks of age
• exercised mice show reduced ejection fraction and fractional shortening compared to exercised wild-type mice
• SB216763 treatment improves cardiac function
|
• mice develop cardiomyopathy by 8 weeks of age
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• exercised mice show numerous TUNEL+ nuclei in the myocardium indicating increased apoptosis compared to exercised wild-type mice
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cellular
• exercised mice show numerous TUNEL+ nuclei in the myocardium indicating increased apoptosis compared to exercised wild-type mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
arrhythmogenic right ventricular dysplasia 10 | DOID:0110081 |
OMIM:610193 |
J:235770 |