A Heterozygous Mutation in Cardiac Troponin T Promotes Ca2+ Dysregulation and Adult Cardiomyopathy in Zebrafish.

ABSTRACT: Cardiomyopathies are a group of heterogeneous diseases that affect the muscles of the heart, leading to early morbidity and mortality in young and adults. Genetic forms of cardiomyopathy are caused predominantly by mutations in structural components of the cardiomyocyte sarcomeres, the contractile units of the heart, which includes cardiac Troponin T (TnT). Here, we generated mutations with CRISPR/Cas9 technology in the zebrafish tnnt2a gene, encoding cardiac TnT, at a mutational "hotspot" site to establish a zebrafish model for genetic cardiomyopathies. We found that a heterozygous tnnt2a mutation deleting Arginine at position 94 and Lysine at position 95 of TnT causes progressive cardiac structural changes resulting in heart failure. The cardiac remodeling is presented by an enlarged atr

SUBMITTER: Kamel SM 

PROVIDER: S-EPMC8072640 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature