A truncation in the Aryl Hydrocarbon Receptor of the CRL:WI(Han) rat does not affect the developmental toxicity of TCDD

Jiang, tao; Bell, David Robert; Clode, Sally; Fan, MingQi; Fernandes, Alwyn; Foster, Paul M.D.; Loizou, George; MacNicoll, Alan; Miller, Brian G.; Rose, Martin; Tran, Lang; White, Shaun

Abstract

The Aryl Hydrocarbon Receptor (AhR) is required for the toxicity of TCDD, and so the AhR of CRL:WI and CRL:WI(Han) rats was characterised. Western blot showed AhR proteins of ~110 and ~97 kDa in individual rats from both strains. The AhR cDNA from a CRL:WI(Han) rat with the ~110kDa protein revealed a sequence that was identical to that of the CRL:WI and SD rat. However, cloning of the AhR from a rat with the ~97kDa protein revealed a point mutation, and
five variants encoding two C-terminally truncated variants of the AhR protein, arising from a point mutation in the intron/exon junction and consequent differential splicing. These C-terminally truncated variants were expressed and shown to give rise to a protein of ~97kDa; the recombinant
AhR bound TCDD with an affinity that was not statistically different from the full-length protein. A single-nucleotide polymorphism (SNP) assay was developed, and showed that
both alleles were represented in a Hardy-Weinberg equilibrium in samples of CRL:WI and CRL:WI(Han) populations; both alleles are abundant. Rats from two studies of TCDD developmental toxicity were genotyped, and the association with toxicity investigated using statistical
analysis. There was no plausible evidence that the AhR allele had a significant effect on the toxic endpoints examined. These data show that the two AhR alleles are common in two strains of Wistar rat, and that the AhR alleles had no effect on TCDD-induced developmental toxicity in two independent studies.

Citation

Jiang, T., Bell, D. R., Clode, S., Fan, M., Fernandes, A., Foster, P. M., …White, S. (2009). A truncation in the Aryl Hydrocarbon Receptor of the CRL:WI(Han) rat does not affect the developmental toxicity of TCDD. Toxicological Sciences, 107(2), https://doi.org/10.1093/toxsci/kfn252

• Journal Article Type: Article
• Publication Date: Feb 1, 2009
• Deposit Date: Jun 17, 2010
• Publicly Available Date: Jun 17, 2010
• Journal: Toxicological Sciences
• Print ISSN: 1096-6080
• Electronic ISSN: 1096-6080
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 107
• Issue: 2
• DOI: https://doi.org/10.1093/toxsci/kfn252
• Public URL: https://nottingham-repository.worktribe.com/output/1013959
• Publisher URL: http://toxsci.oxfordjournals.org/cgi/content/abstract/107/2/512?etoc