TISSUE-SPECIFIC EXPRESSION OF THE RAT AH-RECEPTOR AND ARNT MESSENGER-RNAS

The Ah-receptor (AHR) is a ligand activated transcription factor that mediates the biological effects of agonists such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. Upon binding agonists, the AHR dimerizes with a structurally related protein known as ARNT and this heterodimer then binds cognate enhancer elements and activates the expression of target genes. In this report we describe the cloning of the rat AHR cDNA and a fragment of the rat ARNT cDNA for use as probes in ribonuclease protection analysis. Ribonuclease protection analysis indicated that the rat AHR mRNA is expressed at the highest levels in the lung > thymus > kidney > liver while lower levels were expressed in heart and spleen. The rat AHR and ARNT mRNAs were expressed in a largely coordinate manner across the eight tissues examined with the exception of the placenta where AHR levels were relatively low compared to ARNT. In these experiments, a rare splice variant of the AHR was cloned that encoded a protein with a deletion in the ligand binding domain. In vitro expression studies demonstrated that in contrast to the full length AHR, the splice variant did not bind ligand nor did it bind to a cognate enhancer element in the presence of ARNT.