Phenotypes Associated with This Genotype

Genotype
MGI:3622299

• Allelic Composition: Tg(Myh6-Tmod1)65Msus/Tg(Myh6-Tmod1)65Msus
• Genetic Background: involves: FVB/N

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:107823 )

• mutants always die if overstressed with physical handling

premature death ( J:107823 )

• mutants with most severe phenotypes show cardiomyopathic changes between 2 and 4 weeks after birth and die within 2-3 days of exhibiting the phenotypes

cardiovascular system

abnormal heart morphology ( J:107823 )

• percentage of cell volume occupied by the nucleus in hearts is significantly greater, however do not exhibit an increase in nuclear number

abnormal myocardial fiber morphology ( J:107823 )

• myofibrils are disorganized, show a loss of parallel alignment, are curved with distorted Z bands, and exhibit sarcomeric dysgenesis, with a 53% reduction in sarcomeric length

• actin and myosin filaments are found without discernible Z bands is some areas, whereas in other regions distinct closely spaced sarcomeres are seen

myocardial fiber degeneration ( J:107823 )

• myofibrils are absent from large areas of the cell and numerous mitochondria are present, consistent with degenerating cardiomyocytes

thin myocardium ( J:107823 )

• the right ventricular myocardial wall is translucent, indicating a decrease in thickness and the left ventricular posterior wall is thinner

increased heart weight ( J:107823 )

abnormal heart ventricle morphology ( J:107823 )

• ventricular wall shows karyomegalic nuclei

thin interventricular septum ( J:107823 )

• thinning of ventricular septum

dilated heart left ventricle ( J:107823 )

• extreme left ventricle dilation despite the thinned myocardium

abnormal cardiovascular system physiology ( J:107823 )

dilated cardiomyopathy ( J:107823 )

• exhibit global dilation with marked right side atrial and ventricular enlargement, however do not exhibit cardiac hypertrophy

decreased cardiac output ( J:107823 )

decreased cardiac muscle contractility ( J:107823 )

• 59% decrease in +dP/dt, indicating reduced contractility

decreased heart left ventricle muscle contractility ( J:107823 )

• left ventricle exhibits decreased shortening fraction and velocity of circumferential fiber shortening

abnormal cardiac muscle relaxation ( J:107823 )

• 52% decrease in -dP/dt, indicating that relaxation is prolonged

decreased heart rate ( J:107823 )

• heart rate is 11% lower than controls

congestive heart failure ( J:107823 )

• some exhibit heart failure at 2-4 weeks of age

muscle

abnormal myocardial fiber morphology ( J:107823 )

• myofibrils are disorganized, show a loss of parallel alignment, are curved with distorted Z bands, and exhibit sarcomeric dysgenesis, with a 53% reduction in sarcomeric length

• actin and myosin filaments are found without discernible Z bands is some areas, whereas in other regions distinct closely spaced sarcomeres are seen

myocardial fiber degeneration ( J:107823 )

• myofibrils are absent from large areas of the cell and numerous mitochondria are present, consistent with degenerating cardiomyocytes

thin myocardium ( J:107823 )

• the right ventricular myocardial wall is translucent, indicating a decrease in thickness and the left ventricular posterior wall is thinner

dilated cardiomyopathy ( J:107823 )

• exhibit global dilation with marked right side atrial and ventricular enlargement, however do not exhibit cardiac hypertrophy

decreased cardiac muscle contractility ( J:107823 )

• 59% decrease in +dP/dt, indicating reduced contractility

decreased heart left ventricle muscle contractility ( J:107823 )

• left ventricle exhibits decreased shortening fraction and velocity of circumferential fiber shortening

abnormal cardiac muscle relaxation ( J:107823 )

• 52% decrease in -dP/dt, indicating that relaxation is prolonged

vision/eye

exophthalmos ( J:107823 )

• exhibit proptosis with unusually dark eyes

respiratory system

respiratory system phenotype ( J:107823 )

N • normal lungs

homeostasis/metabolism

abnormal atrial thrombosis ( J:107823 )

• thrombi are often present within the left atrium

growth/size/body

increased heart weight ( J:107823 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:107823