CHARACTERIZATION OF A MURINE AHR NULL ALLELE - INVOLVEMENT OF THE AH RECEPTOR IN HEPATIC GROWTH AND DEVELOPMENT

The Ah receptor (AHR) is a ligand-activated transcription factor that mediates a pleiotropic response to environmental contaminants such as benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. In an effort t o gain insight into the physiological role of the AHR and to develop m odels useful In risk assessment, gene targeting was used to inactivate the murine Ahr gene by homologous recombination. Ahr(-1-) mice are vi able and fertile but show a spectrum of hepatic defects that indicate a role for the AHR in normal liver growth and development. The Ahr(-1- ) phenotype is most severe between 0-3 weeks of age and involves slowe d early growth and hepatic defects, including reduced liver weight, tr ansient microvesicular fatty metamorphosis, prolonged extramedullary h ematopoiesis, and portal hypercellularity with thickening and fibrosis .