TitleAHR2 required for normal behavioral responses and proper development of the skeletal and reproductive systems in zebrafish.
Publication TypeJournal Article
Year of Publication2018
AuthorsGarcia, GR, Bugel, SM, Truong, L, Spagnoli, S, Tanguay, R
JournalPLoS One
Volume13
Issue3
Paginatione0193484
Date Published2018
ISSN1932-6203
KeywordsAnimals, Behavior, Animal, Bone Development, CRISPR-Cas Systems, Female, Gene Editing, Gene Expression Regulation, Developmental, Genitalia, Polychlorinated Dibenzodioxins, Receptors, Aryl Hydrocarbon, Reproduction, Zebrafish, Zebrafish Proteins
Abstract

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 (ahr2osu1) 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.

DOI10.1371/journal.pone.0193484
Alternate JournalPLoS ONE
PubMed ID29494622
PubMed Central IDPMC5832240
Grant ListK99 ES025280 / ES / NIEHS NIH HHS / United States
R21 ES025421 / ES / NIEHS NIH HHS / United States
F31 ES026518 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
T32 ES007060 / ES / NIEHS NIH HHS / United States