A truncation in the Aryl Hydrocarbon Receptor of the CRL:WI(Han) rat does not affect the developmental toxicity of TCDD
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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Published: |
Oxford University Press
2009
|
| Online Access: | https://eprints.nottingham.ac.uk/1066/ |
| _version_ | 1848790533406720000 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Jiang, tao |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T18:14:08Z |
| format | Article |
| id | nottingham-1066 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:14:08Z |
| publishDate | 2009 |
| publisher | Oxford University Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-10662020-05-04T20:26:29Z https://eprints.nottingham.ac.uk/1066/ 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 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. Oxford University Press 2009-02 Article PeerReviewed 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 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 http://toxsci.oxfordjournals.org/cgi/content/abstract/107/2/512?etoc doi:10.1093/toxsci/kfn252 doi:10.1093/toxsci/kfn252 |
| spellingShingle | 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 A truncation in the Aryl Hydrocarbon Receptor of the CRL:WI(Han) rat does not affect the developmental toxicity of TCDD |
| title | A truncation in the Aryl Hydrocarbon Receptor of the
CRL:WI(Han) rat does not affect the developmental
toxicity of TCDD |
| title_full | A truncation in the Aryl Hydrocarbon Receptor of the
CRL:WI(Han) rat does not affect the developmental
toxicity of TCDD |
| title_fullStr | A truncation in the Aryl Hydrocarbon Receptor of the
CRL:WI(Han) rat does not affect the developmental
toxicity of TCDD |
| title_full_unstemmed | A truncation in the Aryl Hydrocarbon Receptor of the
CRL:WI(Han) rat does not affect the developmental
toxicity of TCDD |
| title_short | A truncation in the Aryl Hydrocarbon Receptor of the
CRL:WI(Han) rat does not affect the developmental
toxicity of TCDD |
| title_sort | truncation in the aryl hydrocarbon receptor of the
crl:wi(han) rat does not affect the developmental
toxicity of tcdd |
| url | https://eprints.nottingham.ac.uk/1066/ https://eprints.nottingham.ac.uk/1066/ https://eprints.nottingham.ac.uk/1066/ |