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AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish
The aryl hydrocarbon receptor (AHR) is a conserved ligand-activated transcription factor required for proper vertebrate development and homeostasis. The inappropriate activation of AHR by ubiquitous pollutants can lead to adverse effects on wildlife and human health. The zebrafish is a powerful mode...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832240/ https://www.ncbi.nlm.nih.gov/pubmed/29494622 http://dx.doi.org/10.1371/journal.pone.0193484 |
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author | Garcia, Gloria R. Bugel, Sean M. Truong, Lisa Spagnoli, Sean Tanguay, Robert L. |
author_facet | Garcia, Gloria R. Bugel, Sean M. Truong, Lisa Spagnoli, Sean Tanguay, Robert L. |
author_sort | Garcia, Gloria R. |
collection | PubMed |
description | The aryl hydrocarbon receptor (AHR) is a conserved ligand-activated transcription factor required for proper vertebrate development and homeostasis. The inappropriate activation of AHR by ubiquitous pollutants can lead to adverse effects on wildlife and human health. The zebrafish is a powerful model system that provides a vertebrate data stream that anchors hypothesis at the genetic and cellular levels to observations at the morphological and behavioral level, in a high-throughput format. In order to investigate the endogenous functions of AHR, we generated an AHR2 (homolog of human AHR)-null zebrafish line (ahr2(osu1)) using the clustered, regulatory interspaced, short palindromic repeats (CRISPR)-Cas9 precision genome editing method. In zebrafish, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) mediated toxicity requires AHR2. The AHR2-null line was resistant to TCDD-induced toxicity, indicating the line can be used to investigate the biological and toxicological functions of AHR2. The AHR2-null zebrafish exhibited decreased survival and fecundity compared to the wild type line. At 36 weeks, histological evaluations of the AHR2-null ovaries revealed a reduction of mature follicles when compared to wild type ovaries, suggesting AHR2 regulates follicle growth in zebrafish. AHR2-null adults had malformed cranial skeletal bones and severely damaged fins. Our data suggests AHR2 regulates some aspect(s) of neuromuscular and/or sensory system development, with impaired behavioral responses observed in larval and adult AHR2-null zebrafish. This study increases our understanding of the endogenous functions of AHR, which may help foster a better understanding of the target organs and molecular mechanisms involved in AHR-mediated toxicities. |
format | Online Article Text |
id | pubmed-5832240 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58322402018-03-23 AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish Garcia, Gloria R. Bugel, Sean M. Truong, Lisa Spagnoli, Sean Tanguay, Robert L. PLoS One Research Article The aryl hydrocarbon receptor (AHR) is a conserved ligand-activated transcription factor required for proper vertebrate development and homeostasis. The inappropriate activation of AHR by ubiquitous pollutants can lead to adverse effects on wildlife and human health. The zebrafish is a powerful model system that provides a vertebrate data stream that anchors hypothesis at the genetic and cellular levels to observations at the morphological and behavioral level, in a high-throughput format. In order to investigate the endogenous functions of AHR, we generated an AHR2 (homolog of human AHR)-null zebrafish line (ahr2(osu1)) using the clustered, regulatory interspaced, short palindromic repeats (CRISPR)-Cas9 precision genome editing method. In zebrafish, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) mediated toxicity requires AHR2. The AHR2-null line was resistant to TCDD-induced toxicity, indicating the line can be used to investigate the biological and toxicological functions of AHR2. The AHR2-null zebrafish exhibited decreased survival and fecundity compared to the wild type line. At 36 weeks, histological evaluations of the AHR2-null ovaries revealed a reduction of mature follicles when compared to wild type ovaries, suggesting AHR2 regulates follicle growth in zebrafish. AHR2-null adults had malformed cranial skeletal bones and severely damaged fins. Our data suggests AHR2 regulates some aspect(s) of neuromuscular and/or sensory system development, with impaired behavioral responses observed in larval and adult AHR2-null zebrafish. This study increases our understanding of the endogenous functions of AHR, which may help foster a better understanding of the target organs and molecular mechanisms involved in AHR-mediated toxicities. Public Library of Science 2018-03-01 /pmc/articles/PMC5832240/ /pubmed/29494622 http://dx.doi.org/10.1371/journal.pone.0193484 Text en © 2018 Garcia et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Garcia, Gloria R. Bugel, Sean M. Truong, Lisa Spagnoli, Sean Tanguay, Robert L. AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish |
title | AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish |
title_full | AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish |
title_fullStr | AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish |
title_full_unstemmed | AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish |
title_short | AHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish |
title_sort | ahr2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832240/ https://www.ncbi.nlm.nih.gov/pubmed/29494622 http://dx.doi.org/10.1371/journal.pone.0193484 |
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