IMMUNE-SYSTEM IMPAIRMENT AND HEPATIC-FIBROSIS IN MICE LACKING THE DIOXIN-BINDING AH RECEPTOR

The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic an d teratogenic effects of environmentally toxic chemicals such as dioxi n. An AHR-deficient (Ahr(-/-)) mouse line was constructed by homologou s recombination in embryonic stem cells. Almost half of the mice died shortly after birth, whereas survivors reached maturity and were ferti le. 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 fibro sis. Ahr(-/-) mice were also nonresponsive with regard to dioxin-media ted induction of genes encoding enzymes that catalyze the metabolism o f foreign compounds, Thus, the AHR plays an important role in the deve lopment of the liver and the immune system.