Analysis Tools
mortality/aging
|
• high doses of epinephrine in combination with exercise can induce sudden cardiac death in mutants that is not seen in controls
|
|
• susceptibility to postnatal lethality from 1 month of age onwards, with 50% dying within 2 months of age and 100% mortality by 5 months of age
|
cardiovascular system
|
• fatty deposition is seen in the subepicardium, mid-wall region of hearts and in the left ventricle
|
|
• in severely affected regions, hearts show some loss of muscle architecture
|
|
• rupture of desmosomes and loss of myocyte-myocyte adhesion between neighboring cells as indicated by intercellular gaps in hearts
|
|
• defects in intercalated disc integrity as early as 2.5 weeks of age
|
|
• pronounced pockets of fat deposition are seen within the subepicardium of hearts from 6 week old mice
|
|
• 4 week old mice exhibit enlarged hearts
|
|
• right and left ventricular chamber dilation in 4 week old mice which is more pronounced in the right ventricle
|
|
• extensive fibrosis in the heart, seen in the right and left ventricles and in the septum, but not in the atria
|
|
• mice exhibit increased end-diastolic and end-systolic volumes, reduced ejection fraction, and reduced wall thickness in both the right and left ventricle indicating biventricular dilation and depressed systolic function
|
|
• mice exhibit ventricular arrhythmias that are exacerbated with exercise and catecholamine stimulation
• however, mice exhibit normal heart rate
|
|
• spontaneous ectopic premature ventricular contractions
|
|
• epicardial pattern of action potential propagation following ventricular epicardial pacing shows that mutant hearts display pronounced conduction breaks in wavefront propagation within the epicardium
• analysis of action potential propagation in hearts shows prolonged activation time, action potential durations, and action potential dispersion
|
|
• hearts exhibit delayed conduction in the right ventricle following atrial pacing, consistent with right bundle branch block
|
|
• increase in QRS intervals, suggestive of ventricular depolarization delay
|
|
• mice exhibit a severe form of ventricular cardiomyopathy similar to a biventricular form of arrhythmogenic right ventricular cardiomyopathy
|
cellular
|
• hearts show an increase in TUNEL+ cells in the cardiac mid-wall and in the subepicardial region of the heart, indicating increased apoptosis
|
muscle
|
• in severely affected regions, hearts show some loss of muscle architecture
|
|
• rupture of desmosomes and loss of myocyte-myocyte adhesion between neighboring cells as indicated by intercellular gaps in hearts
|
|
• defects in intercalated disc integrity as early as 2.5 weeks of age
|
|
• mice exhibit increased end-diastolic and end-systolic volumes, reduced ejection fraction, and reduced wall thickness in both the right and left ventricle indicating biventricular dilation and depressed systolic function
|
|
• mice exhibit a severe form of ventricular cardiomyopathy similar to a biventricular form of arrhythmogenic right ventricular cardiomyopathy
|
|
• loss or thickening of Z-lines in severely affected regions of the heart
|
growth/size/body
|
• 4 week old mice exhibit enlarged hearts
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| arrhythmogenic right ventricular dysplasia 8 | DOID:0110076 |
OMIM:607450 |
J:205990 | |
