Modeling GATAD1-Associated Dilated Cardiomyopathy in Adult Zebrafish
AbstractAnimal 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. View Full-Text
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Yang, J.; Shah, S.; Olson, T.M.; Xu, X. Modeling GATAD1-Associated Dilated Cardiomyopathy in Adult Zebrafish. J. Cardiovasc. Dev. Dis. 2016, 3, 6.
Yang J, Shah S, Olson TM, Xu X. Modeling GATAD1-Associated Dilated Cardiomyopathy in Adult Zebrafish. Journal of Cardiovascular Development and Disease. 2016; 3(1):6.Chicago/Turabian Style
Yang, Jingchun; Shah, Sahrish; Olson, Timothy M.; Xu, Xiaolei. 2016. "Modeling GATAD1-Associated Dilated Cardiomyopathy in Adult Zebrafish." J. Cardiovasc. Dev. Dis. 3, no. 1: 6.
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