A post-developmental genetic screen for zebrafish models of inherited liver disease.
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 prevalenc...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4423964?pdf=render |
| _version_ | 1817994763903696896 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Seok-Hyung Kim |
| collection | DOAJ |
| description | 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-scale mutant 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. From 250 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 identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease. |
| first_indexed | 2024-04-14T01:56:33Z |
| format | Article |
| id | doaj.art-af2fa58e45da47c8b8fc7fd6c834cb62 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T01:56:33Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-af2fa58e45da47c8b8fc7fd6c834cb622022-12-22T02:19:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012598010.1371/journal.pone.0125980A post-developmental genetic screen for zebrafish models of inherited liver disease.Seok-Hyung KimShu-Yu WuJeong-In BaekSoo Young ChoiYanhui SuCharles R FlynnJoshua T GamseKevin C EssGary HardimanJoshua H LipschutzNaji N AbumradDon C RockeyNonalcoholic 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-scale mutant 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. From 250 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 identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease.http://europepmc.org/articles/PMC4423964?pdf=render |
| spellingShingle | 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 A post-developmental genetic screen for zebrafish models of inherited liver disease. PLoS ONE |
| title | A post-developmental genetic screen for zebrafish models of inherited liver disease. |
| title_full | A post-developmental genetic screen for zebrafish models of inherited liver disease. |
| title_fullStr | A post-developmental genetic screen for zebrafish models of inherited liver disease. |
| title_full_unstemmed | A post-developmental genetic screen for zebrafish models of inherited liver disease. |
| title_short | A post-developmental genetic screen for zebrafish models of inherited liver disease. |
| title_sort | post developmental genetic screen for zebrafish models of inherited liver disease |
| url | http://europepmc.org/articles/PMC4423964?pdf=render |
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