Phenotypes Associated with This Genotype

Genotype
MGI:5645529

• Allelic Composition: Tarbp2^tm1.1Dzw/Tarbp2^tm1.1Dzw; Tg(Tnnt2-cre)5Blh/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2J

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

mortality/aging

premature death ( J:222613 )

• Although homozygotes are born in normal mendelian ratio indicating no embryonic lethality, more than 80 percent of these cardiac conditional knockout homozygotes die by 4 months of age and none survive beyond 8 months of age

cardiovascular system

cardiac fibrosis ( J:222613 )

dilated heart ( J:222613 )

• although gross morphology of the heart is normal at 2 weeks of age, atrial dilation is found by 3 weeks of age and substantial dilation of both atrial and ventricular chambers is found by 1 month of age and is severe in the homozygotes that survive to 2 months of age, yet cardiomyocyte size appears normal

• neonatal adeno-associated virus-mediated delivery of Tarbp2 or transgenic expression of Mir208a suppresses chamber dilation, permits normal cardiac morphology and restores viability as does knockdown of Sox6, while Tnnt2-dirven viral-mediated overexpression of Sox6 recapitulates the phenotype of cardiac conditional null Tarbp2

dilated heart atrium ( J:222613 )

• by 3 weeks of age atrial dilation is found

dilated heart ventricle ( J:222613 )

• by 1 month of age dilation of the ventricular chambers is also found

dilated cardiomyopathy ( J:222613 )

decreased heart left ventricle muscle contractility ( J:222613 )

• by 2 weeks of age the left ventricular fractional shortening is decreased and this drops precipitously resulting in severe systolic dysfunction by 1 month of age

muscle

dilated cardiomyopathy ( J:222613 )

decreased heart left ventricle muscle contractility ( J:222613 )

• by 2 weeks of age the left ventricular fractional shortening is decreased and this drops precipitously resulting in severe systolic dysfunction by 1 month of age