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Genetic Differences in Sensitivity to Alterations of Mandible Structure Caused by the Teratogen 2,3,7,8-Tetrachlorodibenzo-p-Dioxin

¹ University of North Carolina, Charlotte, North Carolina 28223, USA
² University of Michigan, Ann Arbor, Michigan 48109, USA

Correspondence: Address correspondence to: James M. Keller, Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223; e-mail:jmkeller{at}uncc.edu.

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 TCDD’s effects on mandibles did not correspond with the previously reported sensitivity to TCDD’s 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.

Key Words: dioxin • inbred mice • Ahr • morphology • morphometry • mandible

Abbreviations: TCDD, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin • AHR, Aryl-hydrocarbon receptor • Ahrb, the allele of the Aryl-hydrocarbon receptor with higher ligand affinity • Ahrd, the allele of the Aryl-hydrocarbon receptor with lower ligand affinity • GD, gestation day • T1, treatment group 1 • T2, treatment group 2 • T3, treatment group 3 • SNP, single nucleotide polymorphism

This version was published on December 1, 2008

Toxicologic Pathology, Vol. 36, No. 7, 1006-1013 (2008)
DOI: 10.1177/0192623308327409


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