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The mammalian constitutively active receptor (CAR) is a ligand-activated transcription factor that participates in controlling the expression of cytochrome P450 2B (CYP2B) genes in response to xenobiotics in an organ-specific manner. In the presence of phenobar- bital (PB) or PB-type agents, hepatic CYP2B forms are highly inducible. In contrast, PB-dependent in- creases in the expression of CYP2B activities are rare- ly observed in the lung. Mature CAR mRNA could be detected in the liver of 7-week-old Wistar rats by RT- PCR, while lung CAR mRNA had a 91 bp extra nucle- otide sequence inserted in a coding region of hepatic CAR mRNA. By comparing the full- length sequence of hepatic CAR mRNA, including 5'- and 3'-untrans- lated region (3'-UTR), with the genomic sequence com- pleted in the present study, the genomic structure was clarified to consist of 9 exons and 8 introns, in which the coding region expanded from exon 2 in close to its 5'-end to the first one-third of exon 9 after 159 bp of 5'-UTR in the most frequently obtained cDNA clones. In pulmonary CAR mRNA, intron 6 was not spliced out, implying that the lack of CAR in the lung might in part result from the incomplete splicing of precur- sor mRNA during its maturation.

Role of the Defective Splicing of mRNA in the Lack of Pulmonary Expression of Constitutively Active Receptor in Rat