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Publication : Molecular cloning of a mouse bilirubin/phenol UDP- glucuronosyltransferase (UGT<sub>Br</sub>)

First Author  Kong AN Year  1992
Journal  J Clin Pharmacol Volume  32
Pages  742-67 (Abstr 81) Mgi Jnum  J:14203
Mgi Id  MGI:62377 Citation  Kong AN, et al. (1992) Molecular cloning of a mouse bilirubin/phenol UDP- glucuronosyltransferase (UGTBr). J Clin Pharmacol 32:742-67 (Abstr 81)
abstractText  Full text of Abstract: TWENTY-FIRST ANNUAL ACCP MEETING ABSTRACTS. MOLECULAR CLONING OF A MOUSE BILIRUBIN/PHENOL UDP- GLUCURONOSYLTRANSFERASE (UGTBr). A.-N. Tony Kong, Meihui Ma, and Ida S. Owens*. Division of Clinical Pharmacology, Thomas Jefferson University, Philadelphia, PA; and *Section of Genetic Disorders of Drug Metabolism, HGB, NICHD, NIH, Bethesda, MD. Glucuronidation. catalyzed by UDP-glucuronosyltransferase (UGT) is an important process in the metabolism of many drugs, and endogenous substanccs. UGTs belong to a multigene family, comprises of more than 15 genes in mammals. To date only 1 gene has been cloned in the mouse. In order to understand inter-species differences in glucuronidation of drugs, we sought to clone the orthologous gene of the human encoding for bilirubin/phenol UGT in the mouse. We used a 426 basepairs (bp) kpn1/Xba1 fragment of the human HUG-Brl cDNA (Ritter et al., J. Biol. Chem. 266:1043, 1991) to screen a mouse liver lambda-gt11 cDNA library. Two positive clones were obtained and subcloned into SK Bluescript vector. The sequence of the inserts were determined on double strand DNA by dideoxynucleotide chain termination method using Sequenase. Both clones were sequenced and found to be identical. This clone, called UGTBr contained 1202-bp without an open reading frame and therefore is a partial cDNA. The deduced amino acid was 203 residues with a putative transmembrane hydrophobic domain located at the carboxyl terminus analogous to that of the human and the rat. The translation stop codon is located 5' of the consensus sequences for polyadenylation and a short poly(A)+. Alignment of this gene with the carboxyl domain of the UGTBr for the human and the rat shows 91% and 98% identity at the amino acid level; and 86% and 95% identity at the DNA level. Compared to the other mouse UGTm-1. UGTBr shows only 54% and 58% identity at the amino acid and DNA levels, indicating these 2 genes are from different families. In conclusion we cloned a partial cDNA for the mouse UGTBr which shares very high homology with that of the rat and the human.
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