A post-developmental genetic screen for zebrafish models of inherited liver disease

Seok Hyung Kim, Shu Yu Wu, Jeong In Baek, Soo Young Choi, Yanhui Su, Charles R. Flynn, Joshua T. Gamse, Kevin C. Ess, Gary Hardiman, Joshua H. Lipschutz, Naji N. Abumrad, Don C. Rockey

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scalemutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identifiedmultiple post-developmental mutants and establishes zebrafish as a novel animalmodel for post-developmental inherited liver disease.

Original languageEnglish
Article numbere0125980
JournalPLoS ONE
Volume10
Issue number5
DOIs
Publication statusPublished - 07 May 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Kim, S. H., Wu, S. Y., Baek, J. I., Choi, S. Y., Su, Y., Flynn, C. R., Gamse, J. T., Ess, K. C., Hardiman, G., Lipschutz, J. H., Abumrad, N. N., & Rockey, D. C. (2015). A post-developmental genetic screen for zebrafish models of inherited liver disease. PLoS ONE, 10(5), [e0125980]. https://doi.org/10.1371/journal.pone.0125980