BACKGROUND: The aryl hydrocarbon receptor (AhR or dioxin receptor) is a ligand-activated transcription factor that is considered to mediate pleiotropic biological responses such as teratogenesis, tumour promotion, epithelial hyperplasia and the induction of drug-metabolizing enzymes to environmental contaminants usually represented by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In contrast to the role of AhR in the regulatory mechanism of xenobiotic-metabolizing enzymes, there is no direct proof that the AhR is involved in the teratogenic effects of TCDD. RESULTS: To gain insight into the physiological and teratogenic role of the AhR, we have used gene targeting in mice to disrupt the murine Ahr gene by homologous recombination. Ahr-null mice were viable and fertile and were apparently normal at birth, but displayed a slightly slower growth rate than wild-type mice for the first few weeks of life. When pregnant dams were administered with TCDD by gavage, at a dose of 40 microg/kg body weight at gestation day 12.5, none of the Ahr-null mutant foetuses were sensitive to the teratogenic effects of TCDD, although almost all wild-type foetuses suffered from cleft palate and hydronephrosis. In heterozygous Ahr+/- genotypes, nearly all foetuses suffered from hydronephrosis in response to TCDD treatment, while haplo-insufficiency was observed in the incidence of cleft palate. CONCLUSION: These results clearly show that the AhR is involved in the malformation of the palate and kidney in mouse embryos caused by TCDD and suggests that the mechanism of its involvement differs between the cleft palate and hydronephrosis.

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				K. Oikawa, T. Ohbayashi, J. Mimura, R. Iwata, A. Kameta, K. Evine, K. Iwaya, Y. Fujii-Kuriyama, M. Kuroda, and K. Mukai Dioxin Suppresses the Checkpoint Protein, MAD2, by an Aryl Hydrocarbon Receptor-independent Pathway Cancer Res., August 1, 2001; 61(15): 5707 - 5709. [Abstract] [Full Text] [PDF]

				C. Bonnesen, I. M. Eggleston, and J. D. Hayes Dietary Indoles and Isothiocyanates That Are Generated from Cruciferous Vegetables Can Both Stimulate Apoptosis and Confer Protection against DNA Damage in Human Colon Cell Lines Cancer Res., August 1, 2001; 61(16): 6120 - 6130. [Abstract] [Full Text] [PDF]

				B. Santiago-Josefat, E. Pozo-Guisado, S. Mulero-Navarro, and P. M. Fernandez-Salguero Proteasome Inhibition Induces Nuclear Translocation and Transcriptional Activation of the Dioxin Receptor in Mouse Embryo Primary Fibroblasts in the Absence of Xenobiotics Mol. Cell. Biol., March 1, 2001; 21(5): 1700 - 1709. [Abstract] [Full Text] [PDF]

				S. Shimba, T. Wada, and M. Tezuka Arylhydrocarbon receptor (AhR) is involved in negative regulation of adipose differentiation in 3T3-L1 cells: AhR inhibits adipose differentiation independently of dioxin J. Cell Sci., January 8, 2001; 114(15): 2809 - 2817. [Abstract] [Full Text] [PDF]

				W. H. Powell, R. Bright, S. M. Bello, and M. E. Hahn Developmental and Tissue-Specific Expression of AHR1, AHR2, and ARNT2 in Dioxin-Sensitive and -Resistant Populations of the Marine Fish Fundulus heteroclitus Toxicol. Sci., October 1, 2000; 57(2): 229 - 239. [Abstract] [Full Text] [PDF]

				J. C. Benedict, T.-M. Lin, I. K. Loeffler, R. E. Peterson, and J. A. Flaws Physiological Role of the Aryl Hydrocarbon Receptor in Mouse Ovary Development Toxicol. Sci., August 1, 2000; 56(2): 382 - 388. [Abstract] [Full Text] [PDF]

				S. D. Seidel, V. Li, G. M. Winter, W. J. Rogers, E. I. Martinez, and M. S. Denison Ah Receptor-Based Chemical Screening Bioassays: Application and Limitations for the Detection of Ah Receptor Agonists Toxicol. Sci., May 1, 2000; 55(1): 107 - 115. [Abstract] [Full Text] [PDF]

				Q. Ma, A. J. Renzelli, K. T. Baldwin, and J. M. Antonini Superinduction of CYP1A1 Gene Expression. REGULATION OF 2,3,7,8-TETRACHLORODIBENZO-p-DIOXIN-INDUCED DEGRADATION OF Ah RECEPTOR BY CYCLOHEXIMIDE J. Biol. Chem., April 21, 2000; 275(17): 12676 - 12683. [Abstract] [Full Text] [PDF]

				Q. Ma and K. T. Baldwin 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced Degradation of Aryl Hydrocarbon Receptor (AhR) by the Ubiquitin-Proteasome Pathway. ROLE OF THE TRANSCRIPTION ACTIVATON AND DNA BINDING OF AhR J. Biol. Chem., March 17, 2000; 275(12): 8432 - 8438. [Abstract] [Full Text] [PDF]

				Y. Shimizu, Y. Nakatsuru, M. Ichinose, Y. Takahashi, H. Kume, J. Mimura, Y. Fujii-Kuriyama, and T. Ishikawa Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor PNAS, January 18, 2000; 97(2): 779 - 782. [Abstract] [Full Text] [PDF]

				M. J. Lees and M. L. Whitelaw Multiple Roles of Ligand in Transforming the Dioxin Receptor to an Active Basic Helix-Loop-Helix/PAS Transcription Factor Complex with the Nuclear Protein Arnt Mol. Cell. Biol., August 1, 1999; 19(8): 5811 - 5822. [Abstract] [Full Text] [PDF]

				J. J. Reiners Jr. and R. E. Clift Aryl Hydrocarbon Receptor Regulation of Ceramide-induced Apoptosis in Murine Hepatoma 1c1c7 Cells. A FUNCTION INDEPENDENT OF ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR J. Biol. Chem., January 22, 1999; 274(4): 2502 - 2510. [Abstract] [Full Text] [PDF]

				J. Mimura, M. Ema, K. Sogawa, and Y. Fujii-Kuriyama Identification of a novel mechanism of regulation of Ah (dioxin) receptor function Genes & Dev., January 1, 1999; 13(1): 20 - 25. [Abstract] [Full Text]

				F. J. Gonzalez and P. Fernandez-Salguero The Aryl Hydrocarbon Receptor. Studies Using the AHR-Null Mice Drug Metab. Dispos., December 1, 1998; 26(12): 1194 - 1198. [Abstract] [Full Text]

				N.-L. Ge and C. J. Elferink A Direct Interaction between the Aryl Hydrocarbon Receptor and Retinoblastoma Protein. LINKING DIOXIN SIGNALING TO THE CELL CYCLE J. Biol. Chem., August 28, 1998; 273(35): 22708 - 22713. [Abstract] [Full Text] [PDF]

				T. Baba, J. Mimura, K. Gradin, A. Kuroiwa, T. Watanabe, Y. Matsuda, J. Inazawa, K. Sogawa, and Y. Fujii-Kuriyama Structure and Expression of the Ah Receptor Repressor Gene J. Biol. Chem., August 24, 2001; 276(35): 33101 - 33110. [Abstract] [Full Text] [PDF]

				G. P. Lahvis, S. L. Lindell, R. S. Thomas, R. S. McCuskey, C. Murphy, E. Glover, M. Bentz, J. Southard, and C. A. Bradfield Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice PNAS, September 12, 2000; 97(19): 10442 - 10447. [Abstract] [Full Text] [PDF]