Rescue of a Dilated Cardiomyopathy Mouse Model Caused by a Mutation in Tropomyosin (E54K) by Expression of Slow Skeletal Troponin I

Abstract

Dilated cardiomoypathy (DCM) is a disease characterized by decreased contractility and enlargement of cardiac chambers. We have previously shown that E54K mutation in α-tropomyosin (TM54) reduces myofilament Ca+2 sensitivity and causes DCM. Thus, we hypothesized that sensitization of the myofilament to Ca+2 in early phase of DCM would rescue the phenotype of the disease. Four groups were generated: non-transgenic (NTG), TM54,slow skeletal troponin I (ssTnI) and TM54/ssTnI. To sensitize TM54 myofilament we crossbred TM54 mice with ssTnI expressing mice, which increased Ca+2 sensitivity based on force pCa measurements.