title: Expression profile of hepatic genes in cynomolgus macaques bred in Cambodia, China, and Indonesia: implications for cytochrome P450 genes.
abstract: Cynomolgus macaques, frequently used in drug metabolism studies, are bred mainly in the countries of Asia; however, comparative studies of drug metabolism between cynomolgus macaques bred in these countries have not been conducted. In this study, hepatic gene expression profiles of cynomolgus macaques bred in Cambodia (mfCAM), China (mfCHN), and Indonesia (mfIDN) were analyzed. Microarray analysis revealed that expression of most hepatic genes, including drug-metabolizing enzyme genes, was not substantially different between mfCAM, mfCHN, and mfIDN; only 1.1% and 3.0% of all the gene probes detected differential expression (>2.5-fold) in mfCAM compared with mfCHN and mfIDN, respectively. Quantitative polymerase chain reaction showed that the expression levels of 14 cytochromes P450 (P450s) important for drug metabolism did not differ (>2.5-fold) in mfCAM, mfCHN, and mfIDN, validating the microarray data. In contrast, expression of CYP2B6 and CYP3A4 differed (>2.5-fold, p < 0.05) between cynomolgus (mfCAM, mfCHN, or mfIDN) and rhesus macaques, indicating greater differences in expression of P450 genes between the two lineages. Moreover, metabolic activities measured using 14 P450 substrates did not differ substantially (<1.5-fold) between mfCAM and mfCHN. These results suggest that gene expression profiles, including drug-metabolizing enzyme genes such as P450 genes, are similar in mfCAM, mfCHN, and mfIDN.
authors.affiliation: Drug Safety Research Center, Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Ise
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Sakae
authors.initials: S
authors.lastname: Kohara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamashita
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nagata
authors.forename: Koichiro
authors.initials: K
authors.lastname: Fukuzaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Utoh
authors.forename: Chika
authors.initials: C
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uno
mesh_terms: D000818:Animals; D002160:Cambodia; D002681:China; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D007214:Indonesia; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008252:Macaca fascicularis / Q000254:growth & development / Q000378:metabolism*; D008253:Macaca mulatta / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D012727:Sex Characteristics; D013045:Species Specificity; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System