Expression profile of hepatic genes in cynomolgus macaques bred in Cambodia, China, and Indonesia: implications for cytochrome P450 genes

Drug Metab Pharmacokinet. 2012;27(3):307-16. doi: 10.2133/dmpk.dmpk-11-rg-133. Epub 2011 Dec 13.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cambodia
  • China
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • Gene Expression*
  • Indonesia
  • Liver / enzymology
  • Liver / metabolism
  • Macaca fascicularis / growth & development
  • Macaca fascicularis / metabolism*
  • Macaca mulatta / growth & development
  • Macaca mulatta / metabolism
  • Male
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Phylogeny
  • RNA, Messenger / metabolism
  • Sex Characteristics
  • Species Specificity
  • Up-Regulation

Substances

  • RNA, Messenger
  • Cytochrome P-450 Enzyme System