Phenotypes Associated with This Genotype

Genotype
MGI:5906239

• Allelic Composition: Tg(Myh6-ACTC1*E361G)361.20Sbm/0
• Genetic Background: Not Specified

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

cardiovascular system

dilated cardiomyopathy ( J:242344 )

• adrenergic stimulation with dobutamine results in reduced cardiac reserve with contractile dysfunction leading to a molecular phenotype that indicates dilated cardiomyopathy

• however under normal conditions, mice show no overt cardiac abnormalities at least up to 18 months of age

decreased ventricle muscle contractility ( J:242344 )

• at 12 months of age, end-systolic pressure is lower, speed of ventricle contraction is decreased, but speed of pressure increase is normal, indicating a slower contraction in hearts

• ejection fraction of hearts is lower at 12 months, but not at 4-6 months and 18 months of age

decreased cardiac muscle relaxation ( J:242344 )

• both -dP/dt and Tau of hearts is different from controls at 12 months of age indicating impaired relaxation, although overall cardiac function is not weakened

abnormal heart echocardiography feature ( J:242344 )

• increase in left ventricular internal diameter at the end of diastole in 6 month, but not 4 month old mice

• 6 month old mice injected with dobutamine show decreased septum thickness at end of diastole and end of systole and decreased cardiac output

decreased QRS amplitude ( J:242344 )

• ECG recording of mice under anesthesia shows decreased QRS amplitude at 6 months of age

abnormal myocardial fiber physiology ( J:242344 )

• sliding speed of isolated actin in an in vitro motility assay is 7% lower than in control actin

• calcium-sensitivity of force in papillary muscles is greater than in controls

• calcium-sensitivity of thin filaments is lower

• however, cardiomyocytes show normal contraction amplitude (% shortening), contraction speed or relaxation speed under basal conditions and do not behave differently from controls in response to increased calcium concentration or stimulation frequency

decreased response of heart to induced stress ( J:242344 )

• mice exhibit a reduced response to beta-adrenergic stimulation, with the dobutamine-mediated increases in heart rate, septal thickening,ejection fraction, and cardiac output lower than in controls at 18 months of age

homeostasis/metabolism

decreased response of heart to induced stress ( J:242344 )

• mice exhibit a reduced response to beta-adrenergic stimulation, with the dobutamine-mediated increases in heart rate, septal thickening,ejection fraction, and cardiac output lower than in controls at 18 months of age

muscle

dilated cardiomyopathy ( J:242344 )

• adrenergic stimulation with dobutamine results in reduced cardiac reserve with contractile dysfunction leading to a molecular phenotype that indicates dilated cardiomyopathy

• however under normal conditions, mice show no overt cardiac abnormalities at least up to 18 months of age

decreased ventricle muscle contractility ( J:242344 )

• at 12 months of age, end-systolic pressure is lower, speed of ventricle contraction is decreased, but speed of pressure increase is normal, indicating a slower contraction in hearts

• ejection fraction of hearts is lower at 12 months, but not at 4-6 months and 18 months of age

decreased cardiac muscle relaxation ( J:242344 )

• both -dP/dt and Tau of hearts is different from controls at 12 months of age indicating impaired relaxation, although overall cardiac function is not weakened

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1R		DOID:0110456	OMIM:613424	J:242344