The aryl hydrocarbon receptor - Studies using the AHR-null mice

The aryl hydrocarbon receptor (AHR) is believed to mediate the toxic effect s of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls, and polycyclic aromatic hydrocarbons. AHR is a member of the Per, ARNT, Si m/basic-helix-loop-helix superfamily of ligand-activated transcription fact ors that also harbors the transcription factors involved in the hypoxia res ponse, development of the central nervous system, and day-night adaptations . To investigate the role of AHR in chemical toxicity and carcinogenesis an d to determine any possible function in mammalian development and physiolog ical homeostasis, AHR-null mice were developed, The AHR-null mice were resi stant to the acute toxicity of TCDD and had an altered teratogenic response to this compound. These mice were found to have a number of abnormal pheno types, thus confirming that AHR plays an important developmental and physio logical role. Among the most consistent phenotypes was an altered liver pat hology that was associated with accelerated rates of apoptosis. Evidence su ggests that this may be related to an abnormal accumulation of levels of he patic retinoic acid that cause an activation of transforming growth factor beta, resulting in stimulation of apoptosis, AHR may directly or indirectly control levels of a cytochrome P450 that is responsible for catabolizing r etinoic acid.