PT - JOURNAL ARTICLE AU - Tami L. Thomae AU - Emily A. Stevens AU - Adam L. Liss AU - Norman R. Drinkwater AU - Christopher A. Bradfield TI - The Teratogenic Sensitivity to 2,3,7,8-Tetrachlorodibenzo-<em>p</em>-dioxin Is Modified by a Locus on Mouse Chromosome 3 AID - 10.1124/mol.105.019760 DP - 2006 Mar 01 TA - Molecular Pharmacology PG - 770--775 VI - 69 IP - 3 4099 - http://molpharm.aspetjournals.org/content/69/3/770.short 4100 - http://molpharm.aspetjournals.org/content/69/3/770.full SO - Mol Pharmacol2006 Mar 01; 69 AB - In an effort to understand how genetics can influence individual sensitivity to environmentally induced disease, we performed a linkage analysis to identify murine loci in addition to the Ahr locus that influence the incidence of cleft palate and hydronephrosis in developing mice exposed to the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). Administration of 64 μg/kg dioxin to C57BL/6J (B6) dams at embryonic day 9 (E9) led to palatal clefting and hydronephrosis in nearly 100% of embryos by E17. In contrast, similar exposure of CBA/J (CBA) dams led to cleft palate in only 8% and hydronephrosis in 69% of embryos. To determine the genetic basis for this strain-dependent sensitivity, linkage analyses on the progeny of a B6CBAF1 intercross and a CBA×B6CBAF1 backcross were performed. The incidences of cleft palate and hydronephrosis were assessed and genomic DNA from embryos was analyzed at informative simple sequence length polymorphism (SSLP) markers. One locus segregating with dioxin-induced cleft palate was identified (p &lt; 0.01) and designated as chemically mediated teratogenesis number 1 (Cmt1). The Cmt1 locus is located on chromosome 3.