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Identification and Analysis of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 in Cynomolgus Macaques
Authors:Yasuhiro UNO  Shinya HOSAKA  Hiroshi YAMAZAKI
Abstract:Cytochromes P450 (P450) areimportant for not only drug metabolism and toxicity, but also biosynthesis and metabolismof cholesterol and bile acids, and steroid synthesis. In cynomolgus macaques, widely usedin biomedical research, we have characterized P450 cDNAs, which were isolated as expressedsequence tags of cynomolgus macaque liver. In this study, cynomolgus CYP7A1, CYP17A1,CYP20A1, CYP27A1 and CYP51A1 cDNAs were characterized by sequence analysis, phylogeneticanalysis and tissue expression pattern. By sequence analysis, these five cynomolgus P450shad high sequence identities (94–99%) to the human orthologs in amino acids. Byphylogenetic analysis, each cynomolgus P450 was more closely related to the human orthologas compared with the dog or rat ortholog. By quantitative polymerase chain reaction, amongthe 10 tissue types, CYP7A1 and CYP17A1 mRNAs were preferentially expressed in liver andadrenal gland, respectively. Cynomolgus CYP27A1 and CYP51A1 mRNAs were most abundantlyexpressed in liver and testis, respectively. Cynomolgus CYP20A1 mRNA was expressed in allthe tissues, including brain and liver. Tissue expression patterns of each cynomolgus P450were generally similar to that of the human ortholog. These results suggest the molecularsimilarities of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 between cynomolgus macaquesand humans.
Keywords:cynomolgus monkey   cytochrome P450   sequence analysis   tissue expression
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