Phenotypes Associated with This Genotype

Genotype
MGI:3700949

• Allelic Composition: Tg(Myh6-CASQ2)1Mord/0
• Genetic Background: Not Specified

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

mortality/aging

premature death ( J:79838 )

• all mice die by 16 weeks of age

cardiovascular system

abnormal heart morphology ( J:79838 )

• at 7 and 14 weeks of age, total beta-adrenergic receptor density and the number of high affinity receptors are reduced in hearts

abnormal myocardial fiber morphology ( J:46786 )

• ventricular myocytes are larger and have a distinctive appearance with blurred striations

• myocytes are filled with a large number of membrane-limited vesicles which pervade the entire cell outline, displacing myofibrils and mitochondria

enlarged heart ( J:79838 )

• mice show mild chamber enlargement at 7 weeks of age and severe cardiac enlargement at 14 weeks of age

cardiac hypertrophy ( J:46786 , J:79838 )

• severe hypertrophy, with a 2-fold increase in heart mass and cell size (J:46786)

• mice initially exhibit cardiac hypertrophy (J:79838)

abnormal heart left ventricle morphology ( J:79838 )

• progressive increase in left ventricular mass from 7 to 14 weeks of age

thick ventricular wall ( J:79838 )

• left ventricular wall thickness is increased at 7 weeks of age but at 14 weeks, wall thickness is reduced to normal values

cardiac fibrosis ( J:46786 )

• cardiac hypertrophy is accompanied by focal areas of fibrosis

dilated cardiomyopathy ( J:79838 )

• mice initially exhibit cardiac hypertrophy with only a mild reduction in systolic function that progresses to severe cardiac enlargement and left ventricular dysfunction with premature death

decreased cardiac muscle contractility ( J:79838 )

• mice show progressive deterioration of cardiac function, showing an increase in left ventricular end-diastolic diameter, a decrease in % fractional shortening, and reduction in wall thickness from 7 to 14 weeks

decreased heart ventricle muscle contractility ( J:79838 )

• hearts of 7 week old mice show a blunted response to isoproterenol

decreased heart left ventricle muscle contractility ( J:79838 )

• first derivative of left ventricular pressure rise (LV dP/dt max) is reduced in 7 week old mice, indicating decreased basal contractility

• mice undergoing right atrial pacing to match heart rate to that of wild-type mice do not exhibit an increase in left ventricular dP/dt max but instead a decline

decreased cardiac muscle relaxation ( J:79838 )

• myocardial relaxation assessed by LV dP/dt min is impaired in 7 and 14 week old mice under basal conditions

abnormal heart echocardiography feature ( J:79838 )

• echocardiography indicates increased wall thickness progressing to left ventricular enlargement and severe cardiac dysfunction

decreased left ventricle systolic pressure ( J:79838 )

• left ventricular systolic pressure is only slightly reduced in 7 week old mice and is reduced in 14 week old mice

decreased heart rate ( J:79838 )

• heart rate is lower at base line and with isoproterenol in 7 and 14 week old mice

increased heart rate ( J:46786 )

• cardiac hypertrophy is accompanied by rapid heart rate

abnormal myocardial fiber physiology ( J:46786 )

• in whole cell-clamped myocytes, calcium-channel-gated calcium release from the sarcoplasmic reticulum is suppressed, the frequency of occurrence of spontaneous or calcium current-triggered 'calcium-sparks' is reduced and the spark perimeter is less defined

• caffeine-induced calcium transients and the resultant sodium-calcium exchanger currents are increased 10-fold in myocytes

homeostasis/metabolism

abnormal fluid regulation ( J:46786 )

• fluid retention

abnormal calcium ion homeostasis ( J:46786 )

• in whole cell-clamped myocytes, calcium-channel-gated calcium release from the sarcoplasmic reticulum is suppressed, the frequency of occurrence of spontaneous or calcium current-triggered 'calcium-sparks' is reduced and the spark perimeter is less defined

respiratory system

abnormal respiration ( J:46786 )

• increase in the respiratory rate

muscle

abnormal myocardial fiber morphology ( J:46786 )

• ventricular myocytes are larger and have a distinctive appearance with blurred striations

• myocytes are filled with a large number of membrane-limited vesicles which pervade the entire cell outline, displacing myofibrils and mitochondria

dilated cardiomyopathy ( J:79838 )

• mice initially exhibit cardiac hypertrophy with only a mild reduction in systolic function that progresses to severe cardiac enlargement and left ventricular dysfunction with premature death

decreased cardiac muscle contractility ( J:79838 )

• mice show progressive deterioration of cardiac function, showing an increase in left ventricular end-diastolic diameter, a decrease in % fractional shortening, and reduction in wall thickness from 7 to 14 weeks

decreased heart ventricle muscle contractility ( J:79838 )

• hearts of 7 week old mice show a blunted response to isoproterenol

decreased heart left ventricle muscle contractility ( J:79838 )

• first derivative of left ventricular pressure rise (LV dP/dt max) is reduced in 7 week old mice, indicating decreased basal contractility

• mice undergoing right atrial pacing to match heart rate to that of wild-type mice do not exhibit an increase in left ventricular dP/dt max but instead a decline

decreased cardiac muscle relaxation ( J:79838 )

• myocardial relaxation assessed by LV dP/dt min is impaired in 7 and 14 week old mice under basal conditions

abnormal sarcoplasmic reticulum morphology ( J:46786 )

• junctions between the sarcoplasmic reticulum and the surface membrane, or peripheral couplings, and between the sarcoplasmic reticulum and T tubules are less frequent than in wild-type myocardium

• the junctions are smaller and the junctional sarcoplasmic reticulum is enlarged and the calsequestrin content is more dispersed

growth/size/body

enlarged heart ( J:79838 )

• mice show mild chamber enlargement at 7 weeks of age and severe cardiac enlargement at 14 weeks of age

cardiac hypertrophy ( J:46786 , J:79838 )

• severe hypertrophy, with a 2-fold increase in heart mass and cell size (J:46786)

• mice initially exhibit cardiac hypertrophy (J:79838)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:79838