mortality/aging
• mice subjected to acute beta-adrenergic stimulation using isoproterenol show severe atrioventricular (AV) blocks and die before the end of the experiment
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• mice have a median life span of 20 weeks
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cardiovascular system
• 3-fold increase in the number of gamma-H2AX+ nuclei in cardiac sections indicating an increase in the number of DNA double-strand breaks and an increase in expression of genes related to DNA damage indicating presence of genotoxic stress and DNA damage in hearts
• mice develop cardiac phenotypes early in life, with the main structural and functional cardiac parameters altered by 3 weeks after birth
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• electron-dense nuclear envelope-associated heterochromatin is almost absent in more than 30% of nuclei, indicating chromatin abnormalities
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• cardiomyocytes from 2-month-old mice show increases in length, width, and area
• however, cardiac sections show normal sarcomere ultrastructure
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• hearts show severe dilation of the atrial chambers at 3 months of age
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• hearts show severe dilation of the ventricular chambers at 3 months of age
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• mice show severe dilated cardiomyopathy, characterized by cardiac chamber dilation and reduced ventricular wall thickness
• however, heart weight normalized to tibia length is normal
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• ejection fraction is half that of wild-type mice and fractional shortening is reduced
• however, isolated cardiomyocytes exposed to electrical stimulation (pacing) show normal length of sarcomeres, fractional shortening, diastolic calcium levels, and transient amplitude and time to calcium peak
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• echocardiography shows a decrease in systolic left ventricular anterior wall thickness and a 3-fold increase in systolic left ventricular internal diameter, ejection fraction that is half that of wild-type mice, and reduced fractional shortening
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• cardiac electrical alterations worsen to a type II AV block in a subset of mice, in which P waves are not followed by a QRS complex
• mice subjected to acute beta-adrenergic stimulation using isoproterenol show severe AV blocks and die before the end of the experiment
|
• ECG shows cardiac electrical alterations characterized by an increased P-R interval, suggesting delayed conduction of the electrical signal from the atria to the ventricles through the AV node
• however, no alterations in cardiac rhythm or correct QT duration are seen under basal conditions and morphology and size of the AV node are similar to wild-type
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homeostasis/metabolism
• mice subjected to acute beta-adrenergic stimulation using isoproterenol show severe atrioventricular (AV) blocks and die before the end of the experiment
|
muscle
N |
• no abnormalities in different skeletal muscle groups are seen, including no difference in skeletal muscle weight
|
• electron-dense nuclear envelope-associated heterochromatin is almost absent in more than 30% of nuclei, indicating chromatin abnormalities
|
• cardiomyocytes from 2-month-old mice show increases in length, width, and area
• however, cardiac sections show normal sarcomere ultrastructure
|
• mice show severe dilated cardiomyopathy, characterized by cardiac chamber dilation and reduced ventricular wall thickness
• however, heart weight normalized to tibia length is normal
|
• ejection fraction is half that of wild-type mice and fractional shortening is reduced
• however, isolated cardiomyocytes exposed to electrical stimulation (pacing) show normal length of sarcomeres, fractional shortening, diastolic calcium levels, and transient amplitude and time to calcium peak
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
cardiomyopathy | DOID:0050700 | J:331716 |