Phenotypes Associated with This Genotype

Genotype
MGI:5424158

• Allelic Composition: Dot1l^tm1Tche/Dot1l^tm1.1Tche; Tg(Myhca-cre)1Abel/0
• Genetic Background: Not Specified

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:168140 )

• mice surviving the early postnatal period died by 6 mo of age

postnatal lethality, incomplete penetrance ( J:168140 )

• sudden death was observed in 50% of the mutant mice within 2 wk after birth

cardiovascular system

abnormal heart morphology ( 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

• 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

enlarged heart ( J:168140 )

increased heart weight ( 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

increased heart left ventricle size ( J:168140 )

• conscious ECHOs performed on P10 pups demonstrate that mutant mice have increased left ventricular internal dimensions and volume

dilated heart ventricle ( J:168140 )

• dilation of both heart chambers

cardiac interstitial fibrosis ( J:168140 )

• reactive fibrosis, interstitial

dilated cardiomyopathy ( J:168140 )

decreased cardiac output ( 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

increased fetal cardiomyocyte proliferation ( 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

prolonged RR interval ( J:168140 )

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

atrioventricular block ( J:168140 )

prolonged PR interval ( J:168140 )

prolonged P wave ( J:168140 )

prolonged QRS complex duration ( J:168140 )

cellular

cardiac interstitial fibrosis ( J:168140 )

• reactive fibrosis, interstitial

increased fetal cardiomyocyte proliferation ( 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

increased cardiomyocyte apoptosis ( J:168140 )

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

muscle

abnormal muscle physiology ( J:168140 )

• transmission electron microscopic (TEM) analysis reveals a significant increase of vacuoles in mutant myocytes, suggesting an increase in autophagic cell death

dilated cardiomyopathy ( J:168140 )

increased fetal cardiomyocyte proliferation ( 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

increased cardiomyocyte apoptosis ( J:168140 )

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

growth/size/body

enlarged heart ( J:168140 )

increased heart weight ( 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1A		DOID:0110425	OMIM:115200	J:168140