Background
Mauritian cynomolgus macaques have greatly restricted genetic diversity in the MHC region compared to other nonhuman primates; however the frequency of common MHC haplotypes among captive-bred populations has not been reported.
Methods
Microsatellite PCR was used to determine MHC haplotype frequencies among captive macaques at a UK breeding facility. Allele-specific PCR and Reference Strand Conformational Analysis were used to determine the allele expression profile of a subset of animals.
Results
Haplotypes H3 (21%) and H1 (19%) were most common in the captive population of Mauritian cynomolgus macaques. Predicted alleles were detected by allele-specific PCR-SSP in 99% of animals. Allele expression profiles were similar in animals with identical haplotypes.
Conclusion
Mauritian cynomolgus macaques in the UK breeding facility have restricted MHC diversity comparable to a previously described population. Microsatellite-derived haplotypes are highly predictive of allele expression. A selective breeding program has been established to produce MHC-identical animals for biomedical research.
The genetic and biological similarity between non-human primates and humans has ensured the continued use of primates in biomedical research where other species cannot be used. Health-monitoring programmes for non-human primates provide an approach to monitor and control both endemic and incoming agents that may cause zoonotic and anthroponotic disease or interfere with research outcomes. In 1999 FELASA recommendations were published which aimed to provide a harmonized approach to health monitoring programmes for non-human primates. Scientific and technological progress, understanding of non-human primates and evolving microbiology has necessitated a review and replacement of the current recommendations. These new recommendations are aimed at users and breeders of the commonly used non-human primates; Macaca mulatta (Rhesus macaque) and Macaca fascicularis (Cynomolgus macaque). In addition, other species including Callithrix jacchus (Common marmoset) Saimiri sciureus (Squirrel monkey) and others are included. The important and challenging aspects of non-human primate health-monitoring programmes are discussed, including management protocols to maintain and improve health status, health screening strategies and procedures, health reporting and certification. In addition, information is provided on specific micro-organisms and the recommended frequency of testing.
IntroductionThe cynomolgus monkey is a laboratory primate commonly used as a model for the study of allergic diseases, in particular addressing symptoms, disease mechanisms and treatments for allergic asthma. It has also found use in preclinical toxicology studies of therapeutic agents prior to clinical trials. The choice of cynomolgus monkey as a species for allergic and toxicological evaluations is due to a perceived similarity of primate systems to human biology and to human immunity. However, limited information is available on the biological relevance of these models in relation to IgE immune responses and therapeutics.Antibodies of the IgE class are known to contribute to the body's defense against parasites and toxins, but also to play critical roles in the pathogenesis and potentiation of allergic diseases.1 IgE exerts its biological functions through engagement of its cognate receptors, the low affinity receptor CD23 (K a ~10 Background: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. Ige therapeutics in development depend upon engagement with the FcεrI and FcεrII receptors on immune effector cells for their function. only limited knowledge of the primate Ige immune system is available to inform the choice of models for mechanistic and safety evaluations.Methods: The recognition of human Ige by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays.results: We report cross-reactivity of human Ige Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human Ige dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of Ige-mediated target cell killing, with higher concentrations of human Ige needed to elicit effector response in the cynomolgus monkey system. additionally, human Ige binding on immune effector cells yielded significantly different cytokine release profiles in each species.Conclusion: These data suggest that human Ige binds with different characteristics to human and cynomolgus monkey Ige effector cells. This is likely to affect the potency of Ige effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies.
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