Haploinsufficiency of mechanistic target of rapamycin ameliorates bag3 cardiomyopathy in adult zebrafish.

ABSTRACT: The adult zebrafish is an emerging vertebrate model for studying human cardiomyopathies; however, whether the simple zebrafish heart can model different subtypes of cardiomyopathies, such as dilated cardiomyopathy (DCM), remains elusive. Here, we generated and characterized an inherited DCM model in adult zebrafish and used this model to search for therapeutic strategies. We employed transcription activator-like effector nuclease (TALEN) genome editing technology to generate frame-shift mutants for the zebrafish ortholog of human BCL2-associated athanogene 3 (BAG3), an established DCM-causative gene. As in mammals, the zebrafish bag3 homozygous mutant (bag3^e2/e2 ) exhibited aberrant proteostasis, as indicated by impaired autophagy flux and elevated ubiquitin

SUBMITTER: Ding Y 

PROVIDER: S-EPMC6826022 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature