Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor.
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.
Fernandez-Salguero
P
P
Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Pineau
T
T
Hilbert
D M
DM
McPhail
T
T
Lee
S S
SS
Kimura
S
S
Nebert
D W
DW
Rudikoff
S
S
Ward
J M
JM
Gonzalez
F J
FJ
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007109:Immunity / Q000502:physiology*; D008099:Liver / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000235:genetics / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*
D018336:Receptors, Aryl Hydrocarbon