Isolation and sequencing of rat liver bilirubin UDP-glucuronosyltransferase cDNA: possible alternate splicing of a common primary transcript.

A 1763-bp cDNA for rat liver bilirubin UDP-glucuronosyltransferase (UDPGT) was isolated. Bilirubin UDPGT activity was demonstrated by transfection of the pcDL1 vector carrying the cDNA into COS7 monkey kidney cells. The cDNA shares an identical 913-bp sequence (corresponding to the C-terminal 247 amino acid residues) with that for rat liver 3-methylcholanthrene-inducible 4-nitrophenol UDPGT including the locus where a -1 frameshift mutation was found in the 4-nitrophenol UDPGT cDNA from the jaundiced homozygous Gunn rat. The result suggests that both the UDPGTs are derived from a common primary-transcript and that the multiple defects of UDPGT isoenzymes observed in the homozygous Gunn rat may be produced by a single-mutated-locus after an alternative splicing of the 5' end region.