Phenotypes Associated with This Genotype

Genotype
MGI:5426837

• Allelic Composition: Tg(Myh6-BRUNOL4*)10Coop/0
• Genetic Background: involves: FVB

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

mortality/aging

premature death ( J:99369 )

• premature death is commonly seen in mutants, however mutants do not show overt signs of poor health prior to death

• 91% of males, but only 27% of females are still alive at 24 weeks of age

pregnancy-related premature death ( J:99369 )

• females do not tolerate pregnancy, with females dying during pregnancy

cardiovascular system

abnormal lung vasculature morphology ( J:99369 )

• lungs of affected 9 week old females show dilated veins with muscular hypertrophy of the wall, indicative of chronically elevated left-ventricular-end diastolic pressure

myocardial fiber degeneration ( J:99369 )

• at 3 weeks of age, but not at 4 days of age, females exhibit cardiac fibrosis and myocyte degenerative changes indicative of myocytolysis

• at 9 weeks of age, females exhibit more extensive degenerative myocytolysis, with continuing loss of myofibers and fibrosis

dilated heart left atrium ( J:99369 )

• left atrial dilation is seen at 3 and 9 weeks of age

cardiac hypertrophy ( J:99369 )

• 3 week old females exhibit mild cardiac enlargement that is primarily left side with a globular left ventricular contour

• pregnant females exhibit cardiac hypertrophy, with the heart weight almost 3 times that of control females

• virgin 8 week old females and 9 week old males also exhibit cardiac hypertrophy; heart size of males is not increased as much as in females

• 9 week old females show striking enlarged hearts, with expansion of the chambers but without wall thinning, indicating both cardiac hypertrophy and dilation

• fewer than 50% of males develop cardiac hypertrophy within the first 24 weeks while 85% of females develop cardiac hypertrophy by 6 weeks of age

cardiac fibrosis ( J:99369 )

• at 3 weeks of age, but not at 4 days of age, females exhibit cardiac fibrosis and myocyte degenerative changes indicative of myocytolysis

abnormal cardiovascular system physiology ( J:99369 )

• at 9 weeks of age, females show profound cardiac dysfunction, with an increase in end diastolic and end systolic dimensions

• however, under anesthesia, females have normal heart rates with no sign of persistent arrhythmia

dilated cardiomyopathy ( J:99369 )

• 9 week old females show striking enlarged hearts, with expansion of the chambers but without wall thinning, indicating both cardiac hypertrophy and dilation

decreased diastolic filling velocity ( J:99369 )

• peak early-filling velocity is reduced, whereas the isovolumic relaxation time and Tei index are increased

• no discernible A wave is seen on the transmitral Doppler, indicating that despite the presence of a clear electrical activation of the atria, there is no significant atrial contribution to left-ventricular filling

decreased cardiac muscle contractility ( J:99369 )

• fractional shortening is severely reduced, indicating impaired contraction

• peak aortic flow velocity and mean and peak aortic accelerations are reduced, whereas the isovolumic contraction time is elevated

homeostasis/metabolism

abnormal atrial thrombosis ( J:99369 )

• thrombosis seen in the dilated left atrium at 9 weeks of age is indicative of chronic left-heart dysfunction

muscle

myocardial fiber degeneration ( J:99369 )

• at 3 weeks of age, but not at 4 days of age, females exhibit cardiac fibrosis and myocyte degenerative changes indicative of myocytolysis

• at 9 weeks of age, females exhibit more extensive degenerative myocytolysis, with continuing loss of myofibers and fibrosis

dilated cardiomyopathy ( J:99369 )

• 9 week old females show striking enlarged hearts, with expansion of the chambers but without wall thinning, indicating both cardiac hypertrophy and dilation

decreased cardiac muscle contractility ( J:99369 )

• fractional shortening is severely reduced, indicating impaired contraction

• peak aortic flow velocity and mean and peak aortic accelerations are reduced, whereas the isovolumic contraction time is elevated

respiratory system

abnormal lung morphology ( J:99369 )

• by 9 weeks of age, lungs of affected females look gray and swollen compared to wild-type

abnormal lung vasculature morphology ( J:99369 )

• lungs of affected 9 week old females show dilated veins with muscular hypertrophy of the wall, indicative of chronically elevated left-ventricular-end diastolic pressure

increased lung weight ( J:99369 )

• by 9 weeks of age wet lung weights are more than twice those of wild-type littermates

growth/size/body

cardiac hypertrophy ( J:99369 )

• pregnant females exhibit cardiac hypertrophy, with the heart weight almost 3 times that of control females

• virgin 8 week old females and 9 week old males also exhibit cardiac hypertrophy; heart size of males is not increased as much as in females

• 3 week old females exhibit mild cardiac enlargement that is primarily left side with a globular left ventricular contour

• 9 week old females show striking enlarged hearts, with expansion of the chambers but without wall thinning, indicating both cardiac hypertrophy and dilation

• fewer than 50% of males develop cardiac hypertrophy within the first 24 weeks while 85% of females develop cardiac hypertrophy by 6 weeks of age

increased lung weight ( J:99369 )

• by 9 weeks of age wet lung weights are more than twice those of wild-type littermates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:99369