Towards molecular understanding of species differences in dioxin sensitivity: initial characterization of Ah receptor cDNAs in birds and an amphibian

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated a romatic hydrocarbons (PHAHs) are highly toxic to most vertebrate animals, b ut there are dramatic species differences in sensitivity, both within and a mong vertebrate classes. For example, studies in cultured avian hepatocytes have revealed differential sensitivity of birds to PHAHs [Kennedy et al. ( 1996). Toxicol. Appl. Pharmacol., 141, 214-230]. Differences in the charact eristics or expression of the aryl hydrocarbon receptor (AHR) could contrib ute to these species differences in PHAH responsiveness. To investigate the molecular mechanism of differential PHAH sensitivity, we have begun to cha racterize the AHR in white leghorn chicken (Gallus gallus), Pekin duck (Ana s platyrhynchos), and common tern (Sterna hirundo), as well as an amphibian , mudpuppy (Necturus maculosus). Partial AHR cDNAs encompassing the helix-l oop-helix and PAS domains were cloned and sequenced. Comparison of amino ac id sequences in this region indicated a high degree of sequence conservatio n among the bird species (97% amino acid identity). The percent identity be tween bird sequences and either mouse or mudpuppy was lower (79%); the mudp uppy AHR was 74% identical to the mouse AHR. Phylogenetic analysis of these and other AHR amino acid sequences showed that the bird and mudpuppy AHRs were more closely related to mammalian and fish AHR1 forms than to fish AHR 2. Future studies include the in vitro expression and functional characteri zation of AHRs from these and other non-mammalian vertebrates. (C) 2000 Els evier Science Ltd. All rights reserved.