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Phenotypes Associated with This Genotype
Genotype
MGI:5424158
Allelic
Composition
Dot1ltm1Tche/Dot1ltm1.1Tche
Tg(Myhca-cre)1Abel/0
Genetic
Background
Not Specified
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dot1ltm1.1Tche mutation (0 available); any Dot1l mutation (28 available)
Dot1ltm1Tche mutation (0 available); any Dot1l mutation (28 available)
Tg(Myhca-cre)1Abel mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• sudden death was observed in 50% of the mutant mice within 2 wk after birth (J:168140)
• sudden death was observed in 50% of the mutant mice within 2 wk after birth (J:168140)
• mice surviving the early postnatal period died by 6 mo of age (J:168140)
• mice surviving the early postnatal period died by 6 mo of age (J:168140)

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 (J:168140)
• 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 (J:168140)
• gross changes in heart morphology (such as deviation from an elliptical shape to a more spherical one and increased heart mass) are observed (J:168140)
• 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 (J:168140)
• heart to body weight ratios are increased compared with that of littermate controls; body weight is not significantly altered between controls and mutant mice (J:168140)
• heart to body weight ratios are increased compared with that of littermate controls; body weight is not significantly altered between controls and mutant mice (J:168140)
• conscious ECHOs performed on P10 pups demonstrate that mutant mice have increased left ventricular internal dimensions and volume (J:168140)
• conscious ECHOs performed on P10 pups demonstrate that mutant mice have increased left ventricular internal dimensions and volume (J:168140)
• dilation of both heart chambers (J:168140)
• dilation of both heart chambers (J:168140)
• reactive fibrosis, interstitial (J:168140)
• reactive fibrosis, interstitial (J:168140)
• 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 (J:168140)
• 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 (J:168140)
• 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 (J:168140)
• 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 (J:168140)
• 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 (J:168140)
• 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 (J:168140)
• at P10, TUNEL staining reveals a dramatic increase in apoptotic cell death in mutant hearts compared with the control (J:168140)
• at P10, TUNEL staining reveals a dramatic increase in apoptotic cell death in mutant hearts compared with the control (J:168140)

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 (J:168140)
• 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 (J:168140)
• at P10, TUNEL staining reveals a dramatic increase in apoptotic cell death in mutant hearts compared with the control (J:168140)
• at P10, TUNEL staining reveals a dramatic increase in apoptotic cell death in mutant hearts compared with the control (J:168140)

muscle
• transmission electron microscopic (TEM) analysis reveals a significant increase of vacuoles in mutant myocytes, suggesting an increase in autophagic cell death (J:168140)
• transmission electron microscopic (TEM) analysis reveals a significant increase of vacuoles in mutant myocytes, suggesting an increase in autophagic cell death (J:168140)
• 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 (J:168140)
• 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 (J:168140)
• at P10, TUNEL staining reveals a dramatic increase in apoptotic cell death in mutant hearts compared with the control (J:168140)
• at P10, TUNEL staining reveals a dramatic increase in apoptotic cell death in mutant hearts compared with the control (J:168140)

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


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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
02/02/2016
MGI 6.02
The Jackson Laboratory