Mouse Genome Informatics
cn
    Dot1ltm1Tche/Dot1ltm1.1Tche
Tg(Myhca-cre)1Abel/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• sudden death was observed in 50% of the mutant mice within 2 wk after birth
• mice surviving the early postnatal period died by 6 mo of age

cardiovascular system
• gross changes in heart morphology (such as deviation from an elliptical shape to a more spherical one and increased heart mass) are observed
• RT-qPCR demonstrated that expression of the fetal genes Myh7, Acta1, Nppa, and Nppb is up-regulated in mutant hearts, and adult gene Myh6 is down-regulated indicating reactivation of a fetal gene expression program
• heart to body weight ratios are increased compared with that of littermate controls; body weight is not significantly altered between controls and mutant mice
• conscious ECHOs performed on P10 pups demonstrate that mutant mice have increased left ventricular internal dimensions and volume
• dilation of both heart chambers
• reactive fibrosis, interstitial
• analysis of cardiac output at P10 by measuring ejection fraction and fractional shortening reveals both are reduced by almost half in mutant mice when compared with those of control mice
• the percentage of proliferating cardiomyocyte cells (ratio of Ki-67-positive nuclei to total nuclei, multiplied by 100) is significantly increased in the mutant hearts compared with the control, which may contribute to the observed increase in heart mass
• mutant mice display at least a first-degree heart block at the atrioventricular node, with an 80% penetration of either nonsustained ventricular tachycardia, periodic third- degree heart block, or second-degree Type II heart block
• at P10, TUNEL staining reveals a dramatic increase in apoptotic cell death in mutant hearts compared with the control

cellular
• the percentage of proliferating cardiomyocyte cells (ratio of Ki-67-positive nuclei to total nuclei, multiplied by 100) is significantly increased in the mutant hearts compared with the control, which may contribute to the observed increase in heart mass
• at P10, TUNEL staining reveals a dramatic increase in apoptotic cell death in mutant hearts compared with the control

muscle
• transmission electron microscopic (TEM) analysis reveals a significant increase of vacuoles in mutant myocytes, suggesting an increase in autophagic cell death
• the percentage of proliferating cardiomyocyte cells (ratio of Ki-67-positive nuclei to total nuclei, multiplied by 100) is significantly increased in the mutant hearts compared with the control, which may contribute to the observed increase in heart mass
• at P10, TUNEL staining reveals a dramatic increase in apoptotic cell death in mutant hearts compared with the control

homeostasis/metabolism
• reactive fibrosis, interstitial

Mouse Models of Human Disease
OMIM IDRef(s)
Cardiomyopathy, Dilated, 1A; CMD1A 115200 J:168140