Analysis Tools
mortality/aging
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• older dams exhibit increased mortality likely due to multiple pregnancies-related cardiac remodeling; as a result of this increased mortality, only males were used for further analysis
• occasionally, rare deaths occur during ultrasound handling of mutants, indicating increased susceptibility to adrenergic stress
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cardiovascular system
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• myocardial disarray, which is more prominent in the septum but is also seen to a lesser degree throughout both ventricular walls
• disarray is characterized by a herring-bone, sometimes haphazard pattern of cardiomyocytes
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• hypertrophy is related to increase in the size of individual cardiomyocytes
• cross sectional diameters are increased and mean surface area is increased
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• mineral deposits in fibrotic tissue is seen in the left ventricular subendocardium as early as 4 weeks of age
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• 54% increase in heart weight to body weight ratios at P9.5
• heart weight to tibia length ratio differences reach a maximum of about 2.5-fold difference at 10-12 weeks of age
• mutants develop concentric cardiac hypertrophy but it does not lead to heart failure
• treatment with an inhibitor of Egfr and Erbb2 tyrosine kinases, lapatinib, reduces cardiac hypertrophy
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• diffuse myocardial hypertrophy extending throughout the entire myocardium, with enlarged nuclei
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• left ventricle cavity is smaller during diastole
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• interstitial, perivascular, and endocardial fibrosis that increases with age
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• analysis of cardiovascular physiology was performed in males to preserve females for breeding
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• cardiac output and blood pressure are reduced, but not to a degree that would indicate heart failure
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• reduced fractional shortening; decreases up to 12 months of age but does not decline further thereafter
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• adrenergic stimulation of mutants with isoproterenol induces increased incidence of cardiac arrhythmias (decreased R wave amplitude, widened QRS complex, complex arrhythmias) and sudden death in 100% of mutants compared to wild-type mice which show increased heart rate but do not die and return to normal
• arrhythmias following isoproterenol include atrio-ventricular blocks and in some cases ventricular tachycardia
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• P wave duration varies among mutants, being increased in most mice, biphastic, two-peaked and tall P waves are also common, corresponding to the left and right atria
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• increased QRS complex voltage and duration, left axis deviation, and repolarization abnormalities
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• occasionally, rare deaths occur during ultrasound handling of mutants, indicating increased susceptibility to adrenergic stress
• adrenergic stimulation of mutants with isoproterenol induces increased incidence of cardiac arrhythmias (decreased R wave amplitude, widened QRS complex, complex arrhythmias) and sudden death in 100% of mutants compared to wild-type mice which show increased heart rate but do not die and return to normal
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• cardiac output and blood pressure are reduced, but not to a degree that would indicate heart failure
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• hypertrophic cardiomyopathy; detailed cardiac analysis was carried out only in males to preserve females for breeding
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homeostasis/metabolism
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• occasionally, rare deaths occur during ultrasound handling of mutants, indicating increased susceptibility to adrenergic stress
• adrenergic stimulation of mutants with isoproterenol induces increased incidence of cardiac arrhythmias (decreased R wave amplitude, widened QRS complex, complex arrhythmias) and sudden death in 100% of mutants compared to wild-type mice which show increased heart rate but do not die and return to normal
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muscle
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• myocardial disarray, which is more prominent in the septum but is also seen to a lesser degree throughout both ventricular walls
• disarray is characterized by a herring-bone, sometimes haphazard pattern of cardiomyocytes
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• hypertrophy is related to increase in the size of individual cardiomyocytes
• cross sectional diameters are increased and mean surface area is increased
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• diffuse myocardial hypertrophy extending throughout the entire myocardium, with enlarged nuclei
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• reduced fractional shortening; decreases up to 12 months of age but does not decline further thereafter
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• hypertrophic cardiomyopathy; detailed cardiac analysis was carried out only in males to preserve females for breeding
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growth/size/body
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• 54% increase in heart weight to body weight ratios at P9.5
• heart weight to tibia length ratio differences reach a maximum of about 2.5-fold difference at 10-12 weeks of age
• mutants develop concentric cardiac hypertrophy but it does not lead to heart failure
• treatment with an inhibitor of Egfr and Erbb2 tyrosine kinases, lapatinib, reduces cardiac hypertrophy
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• diffuse myocardial hypertrophy extending throughout the entire myocardium, with enlarged nuclei
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cellular
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hypertrophic cardiomyopathy | DOID:11984 | J:189979 | ||
