The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on molar and mandible traits in congenic mice: A test of the role of the Ahr locus

2,3,7,8-Tetracholorodibenzo-p-dioxin is a highly toxic substance that can cause a variety of adverse effects on organisms. While it has been shown that TCDD acts mainly through the aryl-hydrocarbon receptor (AHR), the mechanism of toxicity is not completely clear. To test the role of the AHR in mediating the effects of TCDD, we exposed two congenic strains of mice differing only at the Ahr locus (Ahrb/Ahrb and Ahrd/Ahrd) to TCDD (0, 0.01, 0, or 1 μg/kg body weight) in utero on gestation day 13 and examined the developmental effects on mandible and mandibular tooth row size and shape. Our hypothesis was that TCDD would significantly affect one or more of these endpoints in Ahrb/Ahrb mice, previously shown to be sensitive to the effects of TCDD, while causing little or no effect in mice carrying the less sensitive Ahrd allele. At the doses used in this study, TCDD did not alter the size of mandibles or molars in either Ahrb/Ahrb or Ahrd/Ahrd mice. However, we did find that the highest dose of TCDD altered mandible shape, but only in Ahrb/Ahrb (not Ahrd/Ahrd) male mice. Similarly, the highest dose of TCDD significantly altered molar shape in Ahrb/Ahrb but not Ahrd/Ahrd male mice, although females in both congenic strains were affected. These results suggest that the effects of TCDD on molar and mandible shape are influenced by the Ahr genotype but that males and females differ in sensitivity to both of these effects.