The genetic composition of populations of cynomolgus macaques (<i><scp>M</scp>acaca fascicularis</i>) used in biomedical research

Kanthaswamy, Sree; Ng, Jillian; Trask, Jessica Satkoski; George, Douglas A.; Kou, Alexander; Hoffman, Lauren; Doherty, T.B.; Houghton, Paul; Smith, David Glenn

doi:10.1111/jmp.12043

Cited by 69 publications

(91 citation statements)

References 61 publications

(117 reference statements)

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“…Animals used in research are sourced from many of these locations and, while subpopulation differences are still minimally studied, potentially important genetic differences between populations are already recognized [21, 22]. Mauritian macaques are attractive for biomedical research for a number of reasons.…”

Section: Introductionmentioning

confidence: 99%

Genetic substructure in cynomolgus macaques (Macaca fascicularis) on the island of Mauritius

Ogawa

Vallender

2014

BMC Genomics

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BackgroundNonhuman primates are commonly used in biomedical research as animal models of human disease and behavior. Compared to common rodent models, nonhuman primates are genetically, physiologically, behaviorally and neurologically more similar to humans owing to more recent shared ancestry and therefore provide the advantage of greater translational validity in preclinical studies. The cynomolgus macaque (Macaca fascicularis) is one of the most commonly used nonhuman primates in academic and industry settings, yet population genetic research has revealed significant substructure throughout the species distribution that may confound studies. Cynomolgus monkeys introduced to Mauritius specifically have previously been thought to maintain the least genetic heterogeneity of all cynomolgus monkeys, although recent work, including work from our lab, suggests macaques from Mauritius too may harbor cryptic substructure.ResultsTo evaluate putative substructure in Mauritian cynomolgus macaques, we designed a panel of 96 single nucleotide polymorphisms based on preliminary findings from previous work to screen 246 of cynomolgus monkeys from two primary suppliers. Results from this study support substructure in Mauritian macaques and suggest a minimum of two populations and maybe three on Mauritius, with moderate admixture.ConclusionThese findings inform the natural history of these monkeys suggesting either a previously unrecognized physical or ecological barrier to gene flow on Mauritius and/or the breakdown of historic substructure resulting from the history of macaque introduction to the island. These findings are relevant to ongoing research using these models in part because of increased appreciation of segregating common variation with functional effects and may be used to better inform animal selection in preclinical research.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-748) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Genetic substructure in cynomolgus macaques (Macaca fascicularis) on the island of Mauritius

Ogawa

Vallender

2014

BMC Genomics

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“…Mauritian cynomolgus macaques (MCM) represent a newer potential model system. MCM originate from the island of Mauritius, and they have limited major histocompatibility complex diversity due to extreme founder effects that created a tight genetic bottleneck (36). Aerosol challenge with M. tuberculosis has been described in these animals (21,37), and they appeared to be quite susceptible to TB.…”

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confidence: 99%

Rhesus Macaques Are More Susceptible to Progressive Tuberculosis than Cynomolgus Macaques: a Quantitative Comparison

et al. 2018

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In the past 2 decades, it has become increasingly clear that nonhuman primates, specifically macaques, are useful models for human tuberculosis (TB). Several macaque species have been used for TB studies, and questions remain about the similarities and differences in TB pathogenesis among macaque species, which can complicate decisions about the best species for a specific experiment. Here we provide a quantitative assessment, using serial positron emission tomography and computed tomography (PET-CT) imaging and precise quantitative determination of bacterial burdens of low-dose Mycobacterium tuberculosis infection in cynomolgus macaques of Chinese origin, rhesus macaques of Chinese origin, and Mauritian cynomolgus macaques. This comprehensive study demonstrates that there is substantial variability in the outcome of infection within and among species. Overall, rhesus macaques have higher rates of disease progression, more lung, lymph node, and extrapulmonary involvement, and higher bacterial burdens than Chinese cynomolgus macaques. The small cohort of Mauritian cynomolgus macaques assessed here indicates that this species is more similar to rhesus macaques than to Chinese cynomolgus macaques in terms of M. tuberculosis infection outcome. These data provide insights into the differences among species, providing valuable data to the field for assessing macaque studies of TB.KEYWORDS Mycobacterium, PET CT, macaque, nonhuman primate, tuberculosis N ovel therapeutics for tuberculosis (TB) are greatly needed to curb the 10.4 million new cases and 1.8 million deaths that occur due to this global pandemic (1). Drugs have aided the fight against TB by saving an estimated 49 million lives between 2000 and 2015 (1). However, the current drug regimen is lengthy and cumbersome, and about 480,000 people developed multidrug-resistant TB in 2015 alone (1), so there is much room for improvement. The only licensed vaccine for TB, Mycobacterium bovis bacillus Calmette-Guérin (BCG), protects infants from severe manifestations of TB but does not provide long-lasting immunity against pulmonary TB (2). The urgent need for new therapeutics for TB has driven the development of novel drugs and vaccines that require preclinical evaluation in animal models. Many animal models are used in TB research, including mice, zebra fish, cattle, rabbits, guinea pigs, and nonhuman primates (NHPs) (3, 4). Mice and NHPs are the two animal models that are the most useful, as the other models suffer from a lack of resources available for immunologic studies. Mice have their shortcomings too, as their TB pathology is not fully representative of the pathology observed in humans, and they do not develop human-like latent TB infection (LTBI). NHPs recapitulate the full spectrum of Mycobacterium tuberculosis

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“…Furthermore, laboratory cynomolgus monkeys of Mauritian origin have been shown to have less genetic diversity than cynomolgus monkeys from across other areas of Asia. 24 Based on these observations, it may be concluded that an IgE antibody therapy introduced into a cynomolgus monkey may not engage in the breadth of binding and functional response seen in the human setting.…”

Section: Discussionmentioning

confidence: 99%

Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

Saul¹,

Josephs²,

Cutler

et al. 2014

mAbs

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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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The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research

Cited by 69 publications

References 61 publications

Genetic substructure in cynomolgus macaques (Macaca fascicularis) on the island of Mauritius

Genetic substructure in cynomolgus macaques (Macaca fascicularis) on the island of Mauritius

Rhesus Macaques Are More Susceptible to Progressive Tuberculosis than Cynomolgus Macaques: a Quantitative Comparison

Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

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