Investigate the effect of cardiomyocyte-specific deletion of Trbp in transaortic constriction model in mice

Cardiac remodeling in response to disease or tissue damage severely impairs heart function. Therefore, the description of the molecular mechanisms responsible is essential for the development of effective therapies. Trbp (Tarbp2) is a multi-functional RNA-binding protein (RBP) that is essential during heart development but its role in the adult heart and cardiac remodeling are unknown. We generated inducible conditional knockout mice to delete Trbp from cardiomyocytes in young adults (Trbp-cKOs). While Trbp-cKO mice did not display a detectable phenotype, under stress conditions induced by transverse aortic constriction (TAC) pressure overload, they rapidly developed severe heart failure; this was associated with maladaptive cardiac remodeling and increased interstitial fibrosis. Trbp-flox/flox (Trbp-fl/fl) mice were generated as previously described. The alpha-MHC-MerCreMer (αMHC-MCM) transgenic mice were purchased from the Jackson Lab and bred with Trbp-fl/fl mice to obtain Trbp-fl/fl-MCM mice. Tamoxifen (TAM) (30mg/kg) was injected once daily for 5 days by intraperitoneal injection into 4-week-old male Trbp-fl/fl-MCM mice to obtain Trbp cardiomyocyte-specific inducible knockout mice (Trbp-cKO). Corn oil was injected as vehicle control into 4-week-old male Trbp-fl/fl-MCM mice. Trbp-fl/fl male mice were also injected with Tamoxifen (30mg/kg for five consecutive days) to control for the potential side effects of Tamoxifen.