title: CYP2G2, pseudogenized in human, is expressed in nasal mucosa of cynomolgus monkey and encodes a functional drug-metabolizing enzyme.
abstract: CYP2G2P is pseudogenized in humans because of two nonsense mutations (c.76C>T in exon 1 and c.382C>T in exon 3) in the putative coding region of the gene sequence, whereas mouse, rat, and rabbit CYP2Gs are expressed and functional in nasal mucosa. In this study, we assessed the intactness of CYP2G in a cynomolgus monkey, a macaque species important for drug metabolism studies because of its evolutionary closeness to human. On the basis of a gene sequence (highly identical to human CYP2G2P) found in the macaque genome, CYP2G2 cDNA was successfully isolated from cynomolgus monkey nasal mucosa. CYP2G2 cDNA, containing an open reading frame of 494 amino acids, was shown to share high sequence identity (nearly 95%) with the putative coding region of human CYP2G2P. Cynomolgus monkey CYP2G2 shared the highest sequence identity (59-61%) with CYP2A23, CYP2A24, and CYP2A26 among cynomolgus monkey cytochromes P450. Cynomolgus monkey CYP2G2 mRNA was predominantly expressed in the nasal mucosa, where CYP2G2 protein expression was also detected. Metabolic assays indicated that cynomolgus monkey CYP2G2 metabolized coumarin, similar to cynomolgus monkey CYP2A23, CYP2A24, and CYP2A26. Moreover, among 39 cynomolgus monkeys and 11 rhesus monkeys examined in this study, only 2 cynomolgus monkeys and 1 rhesus monkey were heterozygous for c.76C>T. No animals carried c.382C>T. These results suggest that cynomolgus monkey CYP2G2 is a functional drug-metabolizing enzyme in nasal mucosa.
authors.affiliation: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories Ltd., 16-1 Minami Akasaka, Kainan, Wakayama 642-0017, Japan. uno-yasuhiro@snbl.co.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uno
authors.forename: Shotaro
authors.initials: S
authors.lastname: Uehara
authors.forename: Norie
authors.initials: N
authors.lastname: Murayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018389:Codon, Nonsense; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D018076:DNA, Complementary; D005091:Exons; D005260:Female; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000378:metabolism*; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats
chemical_list: D018389:Codon, Nonsense; D018076:DNA, Complementary; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System