Phenotypes Associated with This Genotype

Genotype
MGI:5910538

• Allelic Composition: Tg(CMV-cat,-ROCK2*)3-1Koba/0; Tg(Tagln-cre)1Her/0
• Genetic Background: involves: C57BL/6 * C57BL/6JJcl * DBA/2 * SJL

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

mortality/aging

premature death ( J:242116 )

• 34.6% of mice die suddenly by 1 year of age

postnatal lethality, incomplete penetrance ( J:242116 )

• some sudden death of several pups before weaning at 4 weeks of age is seen

cardiovascular system

abnormal aorta morphology ( J:242116 )

• aortas are thinner

abnormal intercalated disk morphology ( J:242116 )

• widening of the gaps at the intercalated discs in the myocardium of 25 week old mice

• desmosomes are less electron-dense than in controls at 25 weeks of age and the gap width at the desmosomes is increased

• distribution of desmosomal proteins is altered

disorganized myocardium ( J:242116 )

• right ventricle shows disorganized myocardial structure with poorly defined cell junctional areas

myocardium steatosis ( J:242116 )

• massive fat accumulation in the right ventricle free wall adjacent to areas of fibrosis is seen in 19 week old mice

increased heart weight ( J:242116 )

• heart weight to body weight ratio is increased

abnormal heart ventricle morphology ( J:242116 )

• ventricular weight to body weight ratio is increased

thin interventricular septum ( J:242116 )

• thinning of interventricular septum of the hearts of E12.5 and E14.5 embryos

abnormal heart right ventricle morphology ( J:242116 )

• massive fat accumulation in the right ventricle free wall adjacent to areas of fibrosis is seen in 19 week old mice

thin ventricular wall ( J:242116 )

• thinning of ventricular walls of the hearts of E12.5 and E14.5 embryos

cardiac fibrosis ( J:242116 )

• myocardial fibrotic changes are first evident at P3 in both the right and left ventricles

• fibrosis is initially seen in epicardial and perivascular regions of the ventricles, progressing to adjacent myocardium with age and involving the entire thickness of the right ventricle free wall at 19 weeks of age

dilated heart ( J:242116 )

• hearts are markedly dilated as early as P3, with dilatation more prominent in the right ventricle and is progressive with age

dilated heart ventricle ( J:242116 )

• progressive ventricular dilatation and thinning from P3

decreased heart left ventricle muscle contractility ( J:242116 )

• reduction in left ventricle ejection fraction and fractional shortening

abnormal fetal cardiomyocyte proliferation ( J:242116 )

• reduction in the number of proliferating cardiomyocytes in the ventricular walls and interventricular septum (both in compact layer and trabeculated layer) in E12.5 hearts

• however, apoptosis levels are normal

abnormal heart echocardiography feature ( J:242116 )

• echocardiography indicates dilated ventricular chambers, increased right ventricle and left ventricle dimensions, and reduced left ventricle ejection fraction and fractional shortening

irregular heartbeat ( J:242116 )

• mice frequently exhibit spontaneous ventricular arrhythmias, evident as long frequent runs of ventricular extrasystoles characterized by widened QRS complexes with no apparent association with the P waves

prolonged PR interval ( J:242116 )

prolonged QRS complex duration ( J:242116 )

abnormal myocardial fiber physiology ( J:242116 )

• reduction in the number of proliferating cardiomyocytes in the ventricular walls and interventricular septum (both in compact layer and trabeculated layer) in adult hearts

decreased systemic arterial systolic blood pressure ( J:242116 )

• systolic blood pressure is lower

ventricular cardiomyopathy ( J:242116 )

• mice develop arrhythmogenic right ventricular cardiomyopathy

cellular

abnormal fetal cardiomyocyte proliferation ( J:242116 )

• reduction in the number of proliferating cardiomyocytes in the ventricular walls and interventricular septum (both in compact layer and trabeculated layer) in E12.5 hearts

• however, apoptosis levels are normal

muscle

abnormal intercalated disk morphology ( J:242116 )

• widening of the gaps at the intercalated discs in the myocardium of 25 week old mice

• desmosomes are less electron-dense than in controls at 25 weeks of age and the gap width at the desmosomes is increased

• distribution of desmosomal proteins is altered

disorganized myocardium ( J:242116 )

• right ventricle shows disorganized myocardial structure with poorly defined cell junctional areas

myocardium steatosis ( J:242116 )

• massive fat accumulation in the right ventricle free wall adjacent to areas of fibrosis is seen in 19 week old mice

decreased heart left ventricle muscle contractility ( J:242116 )

• reduction in left ventricle ejection fraction and fractional shortening

abnormal fetal cardiomyocyte proliferation ( J:242116 )

• reduction in the number of proliferating cardiomyocytes in the ventricular walls and interventricular septum (both in compact layer and trabeculated layer) in E12.5 hearts

• however, apoptosis levels are normal

ventricular cardiomyopathy ( J:242116 )

• mice develop arrhythmogenic right ventricular cardiomyopathy

growth/size/body

increased heart weight ( J:242116 )

• heart weight to body weight ratio is increased

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
arrhythmogenic right ventricular cardiomyopathy		DOID:0050431	OMIM:PS107970	J:242116