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Phenotypes Associated with This Genotype
Genotype
MGI:5660416
Allelic
Composition
Dsptm1Efu/Dsptm1Efu
Myl2tm1(cre)Krc/Myl2+
Genetic
Background
involves: 129 * 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dsptm1Efu mutation (1 available); any Dsp mutation (3 available)
Myl2tm1(cre)Krc mutation (2 available); any Myl2 mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• 4 week old mice exhibit enlarged hearts

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

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
arrhythmogenic right ventricular dysplasia 8 DOID:0110076 OMIM:607450
J:205990


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
02/23/2021
MGI 6.16
The Jackson Laboratory