Phenotypes Associated with This Genotype

Genotype
MGI:5906349

• Allelic Composition: Dicer1^tm1Smr/Dicer1^tm1Smr; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB/N

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

Dilated cardiomyopathy in Dicer1^tm1Smr/Dicer1^tm1Smr Tg(Myh6-cre)2182Mds/0 hearts

growth/size/body

enlarged heart ( J:131962 )

mortality/aging

postnatal lethality, complete penetrance ( J:131962 )

• all mice die within 4 days after birth

behavior/neurological

decreased locomotor activity ( J:131962 )

• pups become fragile and exhibit decreased spontaneous activity preceding death

cardiovascular system

abnormal myocardial fiber morphology ( J:131962 )

• integrity of cardiomyocytes is impaired

disorganized myocardium ( J:131962 )

fetal cardiomyocyte disarray ( J:131962 )

• neonatal cardiomyocytes show disarrayed myofibrils

enlarged heart ( J:131962 )

dilated heart left ventricle ( J:131962 )

dilated cardiomyopathy ( J:131962 )

decreased heart ventricle muscle contractility ( J:131962 )

• decrease in fractional shortening and an increase in the left ventricle posterior wall thickness at end diastole without change at end systole, indicating a loss of ventricle force generation

• hearts exhibit dysregulation of cardiac contractile protein expression

• however, sarcoplasmic reticulum calcium uptake rates are normal in hearts

abnormal heart echocardiography feature ( J:131962 )

• echocardiography indicates severe left ventricle dilation with a decrease in fractional shortening and an increase in the left ventricle posterior wall thickness at end diastole without change at end systole, indicating a loss of ventricle force generation

decreased heart rate ( J:131962 )

• hearts only beat about half of the rate

congestive heart failure ( J:131962 )

cellular

increased cardiomyocyte apoptosis ( J:131962 )

• increase in apoptosis in the left atrium of P2 hearts and in restricted areas of the ventricular apex and left ventricle wall, however no increase in apoptosis is seen before P0

• however, cardiomyocyte proliferation, cell size, and cell number are normal

homeostasis/metabolism

abnormal atrial thrombosis ( J:131962 )

• accumulation of blood clots and/or thrombin in the left atrium

abnormal ventricular thrombosis ( J:131962 )

• accumulation of blood clots and/or thrombin in the left ventricle

muscle

abnormal myocardial fiber morphology ( J:131962 )

• integrity of cardiomyocytes is impaired

disorganized myocardium ( J:131962 )

dilated cardiomyopathy ( J:131962 )

decreased heart ventricle muscle contractility ( J:131962 )

• decrease in fractional shortening and an increase in the left ventricle posterior wall thickness at end diastole without change at end systole, indicating a loss of ventricle force generation

• hearts exhibit dysregulation of cardiac contractile protein expression

• however, sarcoplasmic reticulum calcium uptake rates are normal in hearts

increased cardiomyocyte apoptosis ( J:131962 )

• increase in apoptosis in the left atrium of P2 hearts and in restricted areas of the ventricular apex and left ventricle wall, however no increase in apoptosis is seen before P0

• however, cardiomyocyte proliferation, cell size, and cell number are normal

abnormal sarcomere morphology ( J:131962 )

• less sarcomeres in heart ventricles and the sarcomeres that are present are disarrayed and shorter

• however, intercalated discs appear normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:131962