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

Jiang, tao and Bell, David Robert and Clode, Sally and Fan, MingQi and Fernandes, Alwyn and Foster, Paul M.D. and Loizou, George and MacNicoll, Alan and Miller, Brian G. and Rose, Martin and Tran, Lang and White, Shaun (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). pp. 512-521. ISSN 1096-6080

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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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Biology
Identification Number: 10.1093/toxsci/kfn252
Depositing User: Bell, Dr David R
Date Deposited: 17 Jun 2010 11:43
Last Modified: 14 Oct 2017 12:00
URI: http://eprints.nottingham.ac.uk/id/eprint/1066

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