Identification and Analysis of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1
in Cynomolgus Macaques |
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Authors: | Yasuhiro UNO Shinya HOSAKA Hiroshi YAMAZAKI |
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Abstract: | Cytochromes P450 (P450) are
important for not only drug metabolism and toxicity, but also biosynthesis and metabolism
of cholesterol and bile acids, and steroid synthesis. In cynomolgus macaques, widely used
in biomedical research, we have characterized P450 cDNAs, which were isolated as expressed
sequence tags of cynomolgus macaque liver. In this study, cynomolgus CYP7A1, CYP17A1,
CYP20A1, CYP27A1 and CYP51A1 cDNAs were characterized by sequence analysis, phylogenetic
analysis and tissue expression pattern. By sequence analysis, these five cynomolgus P450s
had high sequence identities (94–99%) to the human orthologs in amino acids. By
phylogenetic analysis, each cynomolgus P450 was more closely related to the human ortholog
as compared with the dog or rat ortholog. By quantitative polymerase chain reaction, among
the 10 tissue types, CYP7A1 and CYP17A1 mRNAs were preferentially expressed in liver and
adrenal gland, respectively. Cynomolgus CYP27A1 and CYP51A1 mRNAs were most abundantly
expressed in liver and testis, respectively. Cynomolgus CYP20A1 mRNA was expressed in all
the tissues, including brain and liver. Tissue expression patterns of each cynomolgus P450
were generally similar to that of the human ortholog. These results suggest the molecular
similarities of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 between cynomolgus macaques
and humans. |
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Keywords: | cynomolgus monkey cytochrome P450 sequence analysis tissue expression |
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