ZFIN ID: ZDB-PUB-170930-11
Modeling GATAD1-Associated Dilated Cardiomyopathy in Adult Zebrafish.
Yang, J., Shah, S., Olson, T.M., Xu, X.
Date: 2016
Source: Journal of cardiovascular development and disease   3(1): (Journal)
Registered Authors: Xu, Xiaolei, Yang, Jingchun
Keywords: TALEN, adult zebrafish, cardiomyopathy, gatad1, transgenic fish
MeSH Terms: none
PubMed: 28955713 Full text @ J Cardiovasc Dev Dis
Animal models have played a critical role in validating human dilated cardiomyopathy (DCM) genes, particularly those that implicate novel mechanisms for heart failure. However, the disease phenotype may be delayed due to age-dependent penetrance. For this reason, we generated an adult zebrafish model, which is a simpler vertebrate model with higher throughput than rodents. Specifically, we studied the zebrafish homologue of GATAD1, a recently identified gene for adult-onset autosomal recessive DCM. We showed cardiac expression of gatad1 transcripts, by whole mount in situ hybridization in zebrafish embryos, and demonstrated nuclear and sarcomeric I-band subcellular localization of Gatad1 protein in cardiomyocytes, by injecting a Tol2 plasmid encoding fluorescently-tagged Gatad1. We next generated gatad1 knock-out fish lines by TALEN technology and a transgenic fish line that expresses the human DCM GATAD1-S102P mutation in cardiomyocytes. Under stress conditions, longitudinal studies uncovered heart failure (HF)-like phenotypes in stable KO mutants and a tendency toward HF phenotypes in transgenic lines. Based on these efforts of studying a gene-based inherited cardiomyopathy model, we discuss the strengths and bottlenecks of adult zebrafish as a new vertebrate model for assessing candidate cardiomyopathy genes.