Cynomolgus and rhesus macaques are non-human primate species widely used in drug metabolism studies. Cynomolgus CYP2C9 (formerly known as CYP2C43) is predominantly expressed in liver and encodes a drug-metabolizing enzyme that metabolizes human CYP2C substrates such as S-mephenytoin and progesterone. In addition, cynomolgus CYP2C9 also metabolizes caffeine, resulting in the formation of the metabolite that is not generated efficiently in humans. Genetic variants of human CYP2C genes account for the inter-individual variability in drug metabolism: however, CYP2C9 variants have not been found in macaques. To see if CYP2C9 is polymorphic in macaques, in this study, CYP2C9 was re-sequenced in 78 cynomolgus and 36 rhesus macaques. A total of 27 non-synonymous variants were found, among which 4 were located in substrate recognition sites, the domain important for protein function. Thirteen and seven variants were unique to cynomolgus and rhesus macaques, respectively. This study revealed the polymorphic nature of cynomolgus and rhesus CYP2C9, similar to human CYP2C genes, by identification of numerous genetic variants including non-synonymous variants.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.dmpk.2014.10.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A study on the variation of cytokine and electrolyte levels in rhesus macaques, cynomolgus monkeys, and Assamese macaques.
Animal Model Exp Med
January 2025
Institute of Medical Biology Chinese Academy of Medical Sciences Peking Union Medical College Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease Medical Primate Research Center, Chinese Academy of Medical Sciences, Kunming, China.
Background: Non-human primates (NPHs), such as rhesus macaques, cynomolgus monkeys, and Assamese macaques, play a crucial role in biomedical research. However, baseline cytokine and electrolyte data for these three species, particularly data stratified by age and sex, are limited. Therefore, the aim of this study was to establish and analyze age- and sex-specific cytokine and electrolyte profiles in these three species.
View Article and Find Full Text PDFEvaluation of dimethandrolone undecanoate in non-human primates as a candidate for long-acting injectable male contraceptive.
Andrology
December 2024
Contraceptive Development Program, Division of Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland, USA.
Background: Dimethandrolone undecanoate (DMAU) is under development as a single agent hormonal male contraceptive. DMAU is a prodrug hydrolyzed by esterase(s) to the active metabolite dimethandrolone (DMA) which has dual androgenic and progestogenic actions. Phase 1 clinical trial results show DMAU to be well-tolerated as an oral contraceptive in healthy men; however, delivery of DMAU as a long-acting injectable rather than a daily oral formulation would provide user compliance benefits and address oral bioavailability concerns.
View Article and Find Full Text PDFA penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates.
Nat Commun
December 2024
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates.
View Article and Find Full Text PDFDevelopment of criteria to optimize manual smear review of automated complete blood counts using a machine learning model.
Vet Clin Pathol
December 2024
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Objective: In this study, we aim to determine if machine learning can reduce manual smear review (MSR) rates while meeting or exceeding the performance of traditional MSR criteria.
Method: 9938 automated CBCs with paired MSRs were performed on samples from rhesus and cynomolgus macaques. The definition of a positive (abnormal) smear was determined.
Spontaneous natural killer cell lymphoproliferative disorder in a rhesus macaque.
J Vet Diagn Invest
January 2025
California National Primate Center, University of California-Davis, Davis, CA, USA.
Lymphoproliferative disorders of natural killer (NK)-cell lineage are well documented in humans but have yet to be documented in non-human primates (NHPs). Here we describe a case of NK-cell lymphoproliferative disorder/leukemia in a 20-y-old captive female rhesus macaque (). The animal clinically had mild splenomegaly and marked lymphocytosis with small-to-medium lymphocytes in blood smears.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!