Differences in UDP-glucuronosyltransferase activities in congenic inbred rats homozygous and heterozygous for the jaundice locus.
The genic transfer of the jaundice locus (jj) from the Gunn rat into the inbred RHA/++ rat produced congenic inbred homozygous RHA/jj rats which lacked detectable bilirubin UDP-glucuronosyltransferase activity. Congenic inbred RHA/j+ rats contained half the activity for bilirubin of the RHA/++ strain. Constitutive activities for glucuronidation of sixteen substrates of twenty-one tested were inherited additively. Approximately seven groups were discernible based on the defect in activity for these substrates in the RHA/jj strain. Activity for 1-hydroxybenzo[a]pyrene was, after that for bilirubin, the most severely reduced (188-fold), while no differences in the glucuronidation of three androgens and of the 6-hydroxy-, 10-hydroxy-, and 11-hydroxybenzo[a]pyrenes were observed. The conjugation of other substrates was affected to an intermediate extent. Most of the twenty-one glucuronidating activities were induced by phenobarbital in the RHA/jj strain as well as in the RHA/++ and RHA/j+ strains. Activities for 9-hydroxybenzo[a]pyrene and for the 2-hydroxy- and 4-hydroxybiphenyls were induced such that the defect was overcome, and the RHA/jj had the same level of activity as the RHA/++ strain. Cytochrome p-450 content and cytochrome c reductase and aminopyrine demethylase activities were unaffected in the congenic strains. Cytochrome p-450 content and cytochrome c reductase activity were induced approximately 2.5- and 2.0-fold, respectively, by phenobarbital while aminopyrine demethylase activity was induced about 30% in each strain. The congenic inbred rats should provide a stable and reproducible genetic model for studying defective UDP-glucuronosyltransferase specified by the jaundice (jj) locus.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D007565:Jaundice / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains
D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase; D009245:NADH Dehydrogenase; D014453:Glucuronosyltransferase