Primate genetics: CYP2C76 PCR test for macaques

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 cytochrome 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.

Prescreening for this null allele reduces variation in drug metabolism profiles in macaques undergoing preclinical trials.

Utilities:

Confirmation of genotype in macaques
Prequalification of rhesus and cynomolgus macaques for preclinical trials

References:
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. Pharmacol. 70:477-486
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.

Specimen requirement: Buccal swab, or 0.2 ml whole blood in EDTA (purple top) or ACD (yellow top) tube.

For specimen types other than those listed here, please call to confirm specimen acceptability and shipping instructions.

For all specimen types, if there will be a delay in shipping, or during very warm weather, refrigerate specimens until shipped and ship with a cold pack unless more stringent shipping requirements are specified. Frozen specimens should be shipped so as to remain frozen in transit. See shipping instructions for more information.

Turnaround time: 2 business days

Methodology: PCR