Phenotypes Associated with This Genotype

Genotype
MGI:5543418

• Allelic Composition: Tg(Myh6-ACTC1*E99K)#Sbm/0
• Genetic Background: involves: C57BL/10 * CBA/Ca

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

mortality/aging

premature death ( J:175388 )

• 48% of females and 22% of males die between 28 and 45 days of age; after this period, survivors show a low level of sporadic mortality that is more prominent in females than males

growth/size/body

enlarged heart ( J:175388 )

• at 29 weeks in females and at 38 weeks in males

cardiac hypertrophy ( J:175388 )

• 21-week old male survivors exhibit hypertrophy in the apical region of the left ventricular posterior wall and interventricular septum

heart left ventricle hypertrophy ( J:175388 )

• 21-week old male survivors exhibit hypertrophy in the apical region of the left ventricular posterior wall and interventricular septum

weight loss ( J:175388 )

• body weight loss becomes evident at 29 weeks in females and 38 weeks in males

cardiovascular system

myocardial fiber disarray ( J:175388 )

• myocyte disarray is seen in ventricular muscle of 21-week old males

increased heart atrium size ( J:175388 )

• 21-week old males exhibit enlarged left and right atria, especially the left atrium

abnormal heart position or orientation ( J:175388 )

• some mutants show hearts in the middle or right side of their chests

enlarged heart ( J:175388 )

• at 29 weeks in females and at 38 weeks in males

cardiac hypertrophy ( J:175388 )

• 21-week old male survivors exhibit hypertrophy in the apical region of the left ventricular posterior wall and interventricular septum

heart left ventricle hypertrophy ( J:175388 )

• 21-week old male survivors exhibit hypertrophy in the apical region of the left ventricular posterior wall and interventricular septum

cardiac interstitial fibrosis ( J:175388 )

• interstitial fibrosis is seen in ventricular muscle of 21-week old male survivors

dilated cardiomyopathy ( J:175388 )

• older mutants (29 week old females and 38 week old males) develop dilated cardiomyopathy with increased end-systolic volume and continuing increased end-diastolic pressure and slower contraction and relaxation rates

decreased cardiac output ( J:175388 )

• in 21-week old males and 29-week old female survivors

decreased cardiac stroke volume ( J:175388 )

• in 21-week old males and 29-week old female survivors

decreased cardiac muscle contractility ( J:175388 )

• end-diastolic volume, stroke volume, ejection fraction, and cardiac output are lower in 21- and 29-week old male and 29-week old female survivors

• contractile response to beta-adrenergic stimulation is reduced, with surviving mutants showing a less pronounced increase in heart rate, wall thickening, and fractional shortening compared with wild-type mice

abnormal cardiac muscle relaxation ( J:175388 )

• myocardial relaxation rates are reduced in surviving mutants

increased left ventricle diastolic pressure ( J:175388 )

• 21-week old male survivors exhibit higher end-diastolic pressure and end-diastolic volume, and reduced end-systolic elastance, although end-systolic pressure is normal

atrial fibrillation ( J:175388 )

• 7 of 8 males and 2 of 5 females at 29-weeks of age show frequent episodes of atrial ectopic fibrillation and atrial flutter at steady status is present in 2 of 8 males and 1 of 5 females

abnormal impulse conducting system conduction ( J:175388 )

• intraventricular conduction abnormalities are seen in 21-week old surviving males

abnormal myocardial fiber physiology ( J:175388 )

• mutants exhibit higher calcium sensitivity in reconstituted thin filaments in an in vitro motility assay and in skinned papillary muscle

congestive heart failure ( J:175388 )

homeostasis/metabolism

pleural effusion ( J:175388 )

• 3 of 5 females and 2 of 5 males exhibit severe hydrothorax with enlarged and dark-colored left atria with scar tissue

muscle

myocardial fiber disarray ( J:175388 )

• myocyte disarray is seen in ventricular muscle of 21-week old males

heart left ventricle hypertrophy ( J:175388 )

• 21-week old male survivors exhibit hypertrophy in the apical region of the left ventricular posterior wall and interventricular septum

dilated cardiomyopathy ( J:175388 )

• older mutants (29 week old females and 38 week old males) develop dilated cardiomyopathy with increased end-systolic volume and continuing increased end-diastolic pressure and slower contraction and relaxation rates

decreased cardiac muscle contractility ( J:175388 )

• end-diastolic volume, stroke volume, ejection fraction, and cardiac output are lower in 21- and 29-week old male and 29-week old female survivors

• contractile response to beta-adrenergic stimulation is reduced, with surviving mutants showing a less pronounced increase in heart rate, wall thickening, and fractional shortening compared with wild-type mice

abnormal cardiac muscle relaxation ( J:175388 )

• myocardial relaxation rates are reduced in surviving mutants

respiratory system

pleural effusion ( J:175388 )

• 3 of 5 females and 2 of 5 males exhibit severe hydrothorax with enlarged and dark-colored left atria with scar tissue

cellular

cardiac interstitial fibrosis ( J:175388 )

• interstitial fibrosis is seen in ventricular muscle of 21-week old male survivors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 11		DOID:0110317	OMIM:612098	J:175388