primate genetic test data sheet
detection of null allele CYP2C76 c.449TG>A in rhesus and
cynomolgus macaques and other species
Macaques are used to study drug metabolism because they
generally show a metabolic pattern similar to humans. Among
enzymes that are involved in drug metabolism, members of the
P450 (P450) family are the most important and
most widely studied. Recently a new P450 gene, CYP2C76, has been
discovered in the livers of cynomolgus and rhesus macaques but
not in humans or the great apes (Uno et al., 2006). CYP2C76
codes for an enzyme that shows unique metabolic activity and is
believed to contribute to overall drug metabolizing activity in
the macaque liver. This enzyme may account for drug metabolism
differences that are sometimes seen between macaques and humans.
A null allele
identified as c.449TG>A was recently identified in CYP2C76
through genetic screening of macaques.
In vitro study has
confirmed that this null allele can abolish the activity of
CYP2C76 (Uno et al., 2009), leading to a different drug
metabolism profile for these monkeys than those carrying other
alleles at this location.
for this null allele reduces variation in drug metabolism
profiles in macaques undergoing preclinical trials.
Help confirm genotype in macaques
Prequalification of rhesus and cynomolgus macaques for
Uno, Y., Fujino, H., Kito, G., Kamataki, T. and Nagata, R.
(2006) CYP2C76, a novel CYP in cynomolgus monkey, is a major
CYP2C in liver, metabolizing tolbutamide and testosterone. Mol.
Uno, Y., Sakuraba, H., Uehara, S.,
Kumano, T., Matsuno, K., Nakamura, C., Kito, G., Kamataki, T.
and Nagata, R. (2009) A null allele impairs function of CYP2C76
gene in cynomolgus monkeys: a possible genetic tool for
generation of a better animal model in drug metabolism. Drug
Metab. Dispos. 37:14-17.
0.2 ml whole blood in EDTA (purple top) or ACD
(yellow top) tube, or buccal swab, or 0.2 ml fresh, frozen or
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