The changes of the cardiac structure and function in cTnTR141W transgenic mice

Objective To establish the transgenic mouse of cTnTR141W gene to make an animal model of dilated cardiomyopathy. Methods A transgenic plasmid was constructed by inserting the cTnTR141W gene driven by the α-MHC promoter. The expression level of the gene was determined with Northern blotting. Pathologic changes were observed by light microscopy and transmission electronic microscopy and analyzed with echocardiography. The localization of the mutant human cTnT protein was detected by immunohistochemistry. The hypertrophy markers were analyzed by RT-PCR. Results Transgenic mice carrying the cTnTR141W mutation were established. The cTnTR141W was expressed by 1.5- to 2.0-fold that of the endogenous cTnT gene and was showed to assemble in the sarcomere. The transgenic heart exhibited a thinner ventricular wall and an enlarged ventricular chamber. Interstitial fibrosis and the elongated and lysed myofrils were also observed in the transgenic heart tissue. The function on EF%, FS% and movement of the ventricular wall was significantly decreased. The immature death occurred after 4 months of age and the immature death rate was 11.1% before 8 months of age in the cTnTR141W mice. The increased NPPB, ACTA1 and decreased ATP2A2 were detected in the transgenic heart. Conclusions The expression of mutant cTnTR141W in the mouse heart caused ventricular chamber enlargement, systolic dysfunction, myocardial hypertrophy, and interstitial fibrosis, suggesting that the cTnTR141W gene is a causal factor for DCM and that the cTnTR141W transgenic mouse is a useful animal model for the study of human DCM.