Analysis of in vitro and in vivo metabolism of zidovudine and gemfibrozil in trans-chromosomic mouse line expressing human UGT2 enzymes.

ABSTRACT: UDP-glucuronosyltransferases (UGTs) catalyze the conjugation of various substrates with sugars. Since the UGT2 family forms a large cluster spanning 1.5 Mb, transgenic mouse lines carrying the entire human UGT2 family have not been constructed because of limitations in conventional cloning techniques. Therefore, we made a humanized mouse model for UGT2 by chromosome engineering technologies. The results showed that six UGT2 isoforms examined were expressed in the liver of adult humanized UGT2 (hUGT2) mice. Thus, the functions of human UGT2B7 in the liver of hUGT2 mice were evaluated. Glucuronide of azidothymidine (AZT, zidovudine), a typical UGT2B7 substrate, was formed in the liver microsomes of hUGT2 mice but not in the liver microsomes of wild-type and Ugt2-knockout mice. When AZT was i

SUBMITTER: Kobayashi K 

PROVIDER: S-EPMC9692130 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature