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Gunn rats lack UDP-glucuronosyltransferase (UDPGT) activity toward bilirubin. 4-Nitrophenol glucuronidation is mediated by several UDPGT isoforms that are distinct from bilirubin-UDPGT, one of which is induced after 3-methylcholanthrene (3-MC) administration in normal, but not in Gunn rats. In normal rats, 3-MC-inducible UDPGT mRNA concentration increased 15-fold in the liver and 3-fold in kidney after 3-MC (140 mg/kg) administration. Concentration of this mRNA is much lower in Gunn rat liver and kidney compared to normal. However, this mRNA was normally induced after 3-MC administration. By RNA blot hybridization, the mRNA in Gunn rat liver and kidney appeared to be of normal size. Nuclear run-on studies showed that the transcription rate for 3-MC-inducible UDPGT was 3-fold higher in Gunn rat liver and kidney than in normal and increased 3- to 5-fold after 3-MC administration. Immunotransblot studies revealed an Mr = 56,000 3-MC-inducible UDPGT in liver and kidney of normal, but not in Gunn rats. However, a new immunoreactive UDPGT band (Mr = 43,000) was present in Gunn, but not in normal rats. Cell-free translation of kidney mRNA from 3-MC-treated Gunn rats showed that the Mr = 43,000 UDPGT is synthesized as an Mr = 45,000 protein. Prior hybridization of the mRNA with an isoform-specific oligonucleotide spanning the initiation codon abolishes synthesis of this protein. These results suggest that a sequence abnormality in the 3-MC-inducible UDPGT mRNA in Gunn rats results in reduced mRNA concentration and synthesis of a truncated, enzymically inactive UDPGT.

Two transgenic mice were produced by microinjection of the entire hepatitis B virus (HBV) genome as a 3.2-kilobase EcoRI DNA fragment into one-cell embryos. Each animal contained a single, unique locus of HBV sequence. One founder animal, G7, contained a partially deleted HBV genome lacking both putative HBV surface antigen (HBsAg) promoters. The other animal, G26, contained greater-than-genome-length HBV sequences organized as a partial head-to-tail dimer. Both transgenic animals transmitted the HBV sequences in a Mendelian fashion, and all subsequent transgenic animals had detectable HBsAg in the serum. Expression of HBV sequences in tissues from G7- and G26-derived mice showed preferential expression of the 2.1-kilobase HBsAg RNA transcript in liver and kidney tissues by Northern (RNA) blot analysis. These data are consistent with the notion that HBV DNA contains cis-acting regulatory sequences which are responsible for the predominant expression of HBsAg transcripts in the liver and kidney of transgenic mice.