Phenotypes Associated with This Genotype

Genotype
MGI:3804498

• Allelic Composition: Tnnt2^tm2Mmto/Tnnt2^tm2Mmto
• Genetic Background: involves: 129S/SvEv * C57BL/6

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

mortality/aging

premature death ( J:137784 )

• high incidence of sudden death in mice particularly between 1 and 3 months of age

• mice die after developing repetitive Torsade des Pointes which degenerates into ventricular defibrillation

• treatment with pimobendan, a Ca²⁺ sensitizer increases life span

cardiovascular system

enlarged heart ( J:137784 )

• increase in size is greater in homozygotes compared to heterozygotes

• treatment with pimobendan, a Ca²⁺ sensitizer decreases heart size

abnormal heart left ventricle morphology ( J:137784 )

• increase in left ventricular end-diastolic dimension

• however, no significant differences in wall thickness are detected

cardiac interstitial fibrosis ( J:137784 )

abnormal cardiovascular system physiology ( J:137784 )

• markers of heart failure are significantly increased by 2 months of age

abnormal cardiac muscle contractility ( J:137784 )

• fractional sarcomere shortening and peak velocity of sarcomere shortening are decreased

decreased heart left ventricle muscle contractility ( J:137784 )

• significant reduction in left ventricular ejection fraction

decreased left ventricle systolic pressure ( J:137784 )

• lower left ventricular end-systolic pressure after administration of isoproterenol

• but, no significant difference in blood pressure of heart rate

prolonged QT interval ( J:137784 )

• electrophysiological abnormalities with long QT

abnormal myocardial fiber physiology ( J:137784 )

• significant increase in cardiomyocyte apoptosis

• decrease in Ca²⁺ sensitivity of force generation with a reduced pCa value at half-maximal force generation

• intact fibers have a decrease in the time to peak force and a steeper rise and fall in force

• faster peak rates of increase and decrease in cytoplasmic Ca²⁺ in intact fibers compared to wild-type controls

• differences are larger in homozygotes compared to heterozygotes

• however, maximum force-generating capabilities and Hill coefficient values are not different from controls and intact fibers show no significant decrease in maximum isometric force per cross-sectional area

muscle

abnormal cardiac muscle contractility ( J:137784 )

• fractional sarcomere shortening and peak velocity of sarcomere shortening are decreased

decreased heart left ventricle muscle contractility ( J:137784 )

• significant reduction in left ventricular ejection fraction

growth/size/body

enlarged heart ( J:137784 )

• increase in size is greater in homozygotes compared to heterozygotes

• treatment with pimobendan, a Ca²⁺ sensitizer decreases heart size

cellular

cardiac interstitial fibrosis ( J:137784 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1D		DOID:0110426	OMIM:601494	J:137784