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Genetic Differences in Sensitivity to Alterations of Mandible Structure Caused by the Teratogen 2,3,7,8-Tetrachlorodibenzo-p-Dioxin
James M. Keller*,
Miriam L. Zelditch,
Yvette M. Huet,
and
Larry J. Leamy
* To whom correspondence should be addressed. E-mail: jmkeller{at}uncc.edu.
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Abstract |
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The contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental pollutant and teratogen that has been shown to alter craniofacial development. Differences in sensitivity to TCDD are attributed primarily to differences in alleles at the Ahr locus coding for the aryl–hydrocarbon receptor (AHR) that binds TCDD and mediates its effects by altering gene expression. The authors used geometric morphometric methods to evaluate differences in the effects of small in utero exposures of TCDD on adult mandible size and shape in five different inbred mouse strains with the same Ahr alleles. Because of the known effects of this toxicant on bone and craniofacial structures, the authors hypothesized that TCDD would decrease mandible size and alter mandible shape, but that the effects of TCDD exposure would differ among the inbred strains. The authors found that TCDD did alter mandible size and shape, but these effects were limited to specific strains and also differed between the sexes. The relative sensitivity to TCDDs effects on mandibles did not correspond with the previously reported sensitivity to TCDDs effects on molars. The authors hypothesize that beyond Ahr-related effects, variation in response to TCDD reflects differences in the genetic architecture controlling the trait being evaluated, thus explaining the species, strain, and trait specificity of TCDD.
First published on November 19, 2008, doi:10.1177/0192623308327409
Toxicologic Pathology 2008;36:1006.
A more recent version of this article appeared on December 1, 2008

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