Next Article in Journal / Special Issue
Drosophila in the Heart of Understanding Cardiac Diseases: Modeling Channelopathies and Cardiomyopathies in the Fruitfly
Previous Article in Journal
Acknowledgement to Reviewers of Journal of Cardiovascular Development and Disease in 2015
Article Menu

Export Article

Open AccessFeature PaperArticle
J. Cardiovasc. Dev. Dis. 2016, 3(1), 6; doi:10.3390/jcdd3010006

Modeling GATAD1-Associated Dilated Cardiomyopathy in Adult Zebrafish

1
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First St. SW Rochester, MN 55905, USA
2
Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, 200 First St. SW Rochester, MN 55905, USA
3
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic College of Medicine, 200 First St. SW Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Georg Vogler and Rolf Bodmer
Received: 1 December 2015 / Revised: 19 January 2016 / Accepted: 22 January 2016 / Published: 26 January 2016
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
View Full-Text   |   Download PDF [1850 KB, uploaded 26 January 2016]   |  

Abstract

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. View Full-Text
Keywords: adult zebrafish; cardiomyopathy; gatad1; TALEN; transgenic fish adult zebrafish; cardiomyopathy; gatad1; TALEN; transgenic fish
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Yang, J.; Shah, S.; Olson, T.M.; Xu, X. Modeling GATAD1-Associated Dilated Cardiomyopathy in Adult Zebrafish. J. Cardiovasc. Dev. Dis. 2016, 3, 6.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Cardiovasc. Dev. Dis. EISSN 2308-3425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top