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Science 5 May 1995:
Vol. 268. no. 5211, pp. 722 - 726
DOI: 10.1126/science.7732381
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Articles

Science, Vol 268, Issue 5211, 722-726
Copyright © 1995 by American Association for the Advancement of Science

articles

Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor

P Fernandez-Salguero, T Pineau, DM Hilbert, T McPhail, SS Lee, S Kimura, DW Nebert, S Rudikoff, JM Ward, and FJ Gonzalez

Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and teratogenic effects of environmentally toxic chemicals such as dioxin. An AHR-deficient (Ahr-/-) mouse line was constructed by homologous recombination in embryonic stem cells. Almost half of the mice died shortly after birth, whereas survivors reached maturity and were fertile. The Ahr-/- mice showed decreased accumulation of lymphocytes in the spleen and lymph nodes, but not in the thymus. The livers of Ahr-/- mice were reduced in size by 50 percent and showed bile duct fibrosis Ahr-/- mice were also nonresponsive with regard to dioxin-mediated induction of genes encoding enzymes that catalyze the metabolism of foreign compounds. Thus, the AHR plays an important role in the development of the liver and the immune system.


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J. Nutr. 133, 277S-281
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Environmental Dioxins and Endometriosis.
S. Rier and W. G. Foster (2002)
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A ligand for the aryl hydrocarbon receptor isolated from lung.
J. Song, M. Clagett-Dame, R. E. Peterson, M. E. Hahn, W. M. Westler, R. R. Sicinski, and H. F. DeLuca (2002)
PNAS 99, 14694-14699
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Interaction with Nedd8, a Ubiquitin-like Protein, Enhances the Transcriptional Activity of the Aryl Hydrocarbon Receptor.
M. Antenos, R. F. Casper, and T. J. Brown (2002)
J. Biol. Chem. 277, 44028-44034
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Effects of Aryl Hydrocarbon Receptor Null Mutation and in Utero and Lactational 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure on Prostate and Seminal Vesicle Development in C57BL/6 Mice.
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P. Andersson, J. McGuire, C. Rubio, K. Gradin, M. L. Whitelaw, S. Pettersson, A. Hanberg, and L. Poellinger (2002)
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J. N. Meyer, D. E. Nacci, and R. T. Di Giulio (2002)
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Recruitment of Dioxin Receptor to Active Transcription Sites.
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S. Wang and O. Hankinson (2002)
J. Biol. Chem. 277, 11821-11827
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Regulatory Interactions among Three Members of the Vertebrate Aryl Hydrocarbon Receptor Family: AHR Repressor, AHR1, and AHR2.
S. I. Karchner, D. G. Franks, W. H. Powell, and M. E. Hahn (2002)
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   Abstract »    Full Text »    PDF »
Subchronic Exposure of [3H]-2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in Female B6C3F1 Mice: Relationship of Steady-State Levels to Disposition and Metabolism.
J. J. Diliberto, M. J. DeVito, D. G. Ross, and L. S. Birnbaum (2001)
Toxicol. Sci. 61, 241-255
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Correlation of Cardiotoxicity Mediated by Halogenated Aromatic Hydrocarbons to Aryl Hydrocarbon Receptor Activation.
S. E. Heid, M. K. Walker, and H. I. Swanson (2001)
Toxicol. Sci. 61, 187-196
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Molecular Regulation of Genes Encoding Xenobiotic-Metabolizing Enzymes: Mechanisms Involving Endogenous Factors.
R. N. Hines, Z. Luo, T. Cresteil, X. Ding, R. A. Prough, J. L. Fitzpatrick, S. L. Ripp, K. C. Falkner, N.-L. Ge, A. Levine, et al. (2001)
Drug Metab. Dispos. 29, 623-633
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Cell-Specific Regulation of Human Aryl Hydrocarbon Receptor Expression by Transforming Growth Factor-{beta}1.
S. Wolff, P. A. Harper, J. M. Y. Wong, V. Mostert, Y. Wang, and J. Abel (2001)
Mol. Pharmacol. 59, 716-724
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Targeted Genomic Disruption of H-ras and N-ras, Individually or in Combination, Reveals the Dispensability of Both Loci for Mouse Growth and Development.
L. M. Esteban, C. Vicario-Abejón, P. Fernández-Salguero, A. Fernández-Medarde, N. Swaminathan, K. Yienger, E. Lopez, M. Malumbres, R. McKay, J. M. Ward, et al. (2001)
Mol. Cell. Biol. 21, 1444-1452
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