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

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Fernandez-Salguero, Pedro | Pineau, Thie | Hilbert, David | Mcphail, Timothy | Lee, Susanna | Kimura, Shioko | Nebert, Daniel | Rudikoff, Stuart | Ward, Jerrold | Gonzalez, Frank

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. 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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