Immune System Impairment and Hepatic Fibrosis in Mice Lacking the Dioxin-Binding Ah Receptor

TLDR

The aryl hydrocarbon receptor mediates carcinogenic and teratogenic effects of environmental toxins like dioxin. AHR-deficient mice were generated via homologous recombination in embryonic stem cells. AHR knockout mice exhibit high neonatal mortality, reduced liver size with bile duct fibrosis, impaired lymphocyte accumulation in spleen and lymph nodes, and loss of dioxin‑induced gene expression, underscoring AHR’s role in liver and immune system development.

Abstract

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.