Macaca fascicularis
(source: Refinements in husbandry, care and common procedures for non-human primates)
Introduction:
The cynomolgus monkey (Macaca fascicularis) is a popular laboratory primate belonging to Old World
monkeys, which are the group most closely related to humans except for the apes.
(reference: Neuroanatomic and magnetic resonance imaging references for normal development of
cerebral sulci of laboratory primate, cynomolgus monkeys (Macaca fascicularis)
The long-tailed macaque is one of the most widely distributed species of nonhuman primates in the
world (Reference: Morphology and somatometric growth of long-tailed macaques in Singapore)
Taxonomy:
The genus Macaca, the Asian representative of Cercopithecine monkeys, is the most widely distributed
nonhuman primate. Its 19 extant species extend from northwestern Africa to a number of islands and
continental areas in southern and eastern Asia Six species exist in China: Macaca mulatta, M. thibetana,
M. assamensis,M. arctoides,M. cyclopis, andM. leonina,of which M. cyclopis and M. thibetana are
endemic. Within Macaca, early studies disagreed on the classification of macaque species groups based
on morphology. Many re-searchers, however, classify the macaques into four species groups (source:
Phylogenetic Relationships of the Macaques (Cercopithecidae: Macaca), Inferred from Mitochondrial
DNA Sequences)
Nine commonly recognized subspecies (M. f. fascicularis, Macaca fascicularis aurea, Macaca fascicularis
condorensis, Macaca fascicularis fusca, Macaca fascicularis karimondjawae, Macaca fascicularis tua,
Macaca fascicularis philippinensis, Macaca fascicularis umbrosa, and Macaca fascicularis lasiae) Among
these subspecies, M. f. fascicularis is the most widely distributed, being found throughout much of the
Indonesian archipelago including Bali, Java, Kalimantan, Sumatra, Sumba, Timor, peninsular Malaysia,
Sabah, Sarawak, Borneo, the Philippines, Singapore, Thailand, and southern Vietnam (Reference:
Macaca fascicularis fascicularis) in Singapore)
Zootechnics:
Except for the breeding colonies of cynomolgus monkeys and vervets at Wake Forest University,
virtually all other large colonies are fed commercial monkey chow, which derives its primary protein
from isoflavone-rich soy meal.
(source: The Unique Value of Primate Models in Translational Research)
Smell and taste:
Because of their role in modulating reproductive physiology and regulating social interactions, it is
important that familiar scents are not totally removed from the captive environments of marmosets and
tamarins during cleaning. Alternate cleaning and sanitation of enclosures and enrichment devices help
to retain scent and has ben- eficial effects on the psychological wellbeing of the animals by reducing
overstimulated scent marking. A small amount of their own used litter carried to a new enclosure for
primates can help to settle them in more quickly.
Taste is important for choosing appropriate foods. Most primates prefer sweet, sugary foods and avoid
bitter or astringent tastes (Hladik
et al. 2002). This is an adaptation to ensure that food is palatable enabling, for example, fruit to be
selected at the right stage of ripeness, since appearance and touch are not always reliable indicators.
(source: Refinements in husbandry, care and common procedures for non-human primates)
Hearing:
Primates have good low-frequency hearing (below 125 Hz) and can hear higher frequency sounds than
humans (Heffner 2004). At 60 dB sound pressure level (SPL), the typical noise level in which people live,
the highest audible frequency for a human is 20 kHz, whereas it is 30 kHz for the common marmoset
and around 40 kHz for the rhesus macaque (Pfingst et al. 1978, Clough 1982). Laboratory sounds at
ultrasonic frequencies could therefore present welfare problems (Clough 1982) and analysis of noise
levels in the laboratory should include ultrasonic frequencies.
(source: Refinements in husbandry, care and common procedures for non-human primates)
Vocalisation:
Primates can readily distinguish between quiet, calm and loud, forceful human voice tones and words,
and this can be useful for training.
(source: Refinements in husbandry, care and common procedures for non-human primates)
Touch and grooming:
Primates have numerous kinds of sensory receptors in their epithelial and connective tissues that are
responsive to sensations such as touch, heat, cold, pressure and pain. They make behavioural choices
based on these sensations. For example, marmosets prefer to use wooden and plastic nest boxes as
opposed to metal ones and this may be related to comfort and temperature (Rumble et al. 2005). They
will respond to soft materials (e.g. fleece) by rubbing their bodies against them.
Tactile contact is very important for primates, especially early in life (Seay et al. 1962, Suomi 1986).
Infants cling to their mothers, and many species huddle together to rest as adults, which probably helps
to promote social cohesion as well as reduce heat loss. Grooming is a very important affiliative
behaviour in primate societies and some species spend up to 20% of each day engaged in this activity
(Dunbar 1991). Grooming relationships are extremely valu- able in helping primates to cope with the
stresses and strains of group life and individual animals will make great efforts to maintain these
relationships in the face of other demands on their time. Grooming also plays a role in keeping the hair
free from parasites and detritus (Hutchins & Barash 1976). It is essential that primate housing is
designed to facilitate these behaviours and includes adequate wide, flat resting surfaces for all the
animals to occupy simultaneously in such a way that they can huddle and groom each other.
Changes in grooming behaviour (e.g. decreased self- grooming leading to an unkempt coat, or increased
groom- ing attention from conspecifics leading to hair loss) may be indicative of a welfare problem
(Honess et al. 2005b).
(source: Refinements in husbandry, care and common procedures for non-human primates)
Recognizing and interpreting primate communication
Being able to recognize, accurately interpret, and respond appropriately to primate communication
signals (both vocalizations and body language) provides a good basis for developing many different
aspects of refinement. It helps in understanding primate behaviour and interactions between individuals
and groups. It is essential for the proper assessment of welfare states, in the recognition and reduction
of any pain or distress, and for facilitating appropriate staff-primate interactions. The easiest signals to
recog- nize are visual signals (e.g. body postures, facial expressions) and vocalizations. These provide
information on a primate’s emotional and physical state, relative social status within the group, and the
animal’s likely response to, and ability to cope with, any given situation or interaction.
Primate facial expressions, body language and behaviours can appear to be similar to those of humans,
but they may have very different meanings and must be interpreted correctly and not in an
anthropomorphic or anthropocentric way. For some signals and behaviours the meaning should be
obvious. An animal that screams, is physically resistant, urinates or passes faeces during a procedure is
clearly frigh- tened, and the procedure should not be continued unless and until the animal has been
given additional habituation, or more specific training, to minimize the fear responses. Other behaviours
are more difficult to interpret. For example, one of the most common expressions seen among primates
is the ‘fear grimace’ or ‘fear grin’, in which the mouth is open and lips retracted. The facial expression is
superficially similar to a human smile, and can be misinterpreted as conveying happiness. In fact, it is a
reaction given by a tense or frightened animal to appease more dominant or aggressive individuals
(including humans) and diffuse tension. Another common source of confusion is the human‘stare’. A
person maystareatan animal out of interest, but most primates will interpret this as an aggressive threat
and respond accordingly. Similarly, facing an animal square on can be taken as a threatening posture.
This ‘mis- communication’ is a common problem when people who have no experience of interacting
with primates visit animal facilities. Primate communication signals are context-specific, and not just
simple, predictable responses. Therefore, it is not possible to attach one rigid meaning to each signal,
and inappropriate to adopt inflexible responses to signals that are given. For example, allogrooming can
reflect several different states. It may indicate that animals are affiliative and relaxed (e.g. Stevenson &
Poole 1976). Alternatively, since allogrooming is known to increase at high population densities and
following conflict in some species, it may indicate that aggression has occurred and be linked to tension
release (e.g. Schinoet al.1988, de Waal 1989, 2000). Allogrooming may also be used to compete for
social contact with, for instance, high-ranking individuals, which may increase tension (Seyfarth 1977).
The posture of the animals in each situation can help to interpret the context. It is therefore important
not to underestimate the knowledge and empathy that is required to communicate well with primates.
The advice of a primate behaviour specialist, perhaps as an
integral part of staff-training, is invaluable in helping staff and animals to interact positively (Box 2).
(source: Refinements in husbandry, care and common procedures for non-human primates)
Assessing and facilitating primate welfare:
Primates are highly intelligent, sentient and social animals with a complex range of emotional as well as
physical needs. There is no question that they have the capacity to experience pain, and unless the
contrary is established, it should be assumed that procedures that cause pain and distress in humans are
likely to cause pain or distress in other primates.
It is also generally accepted that they experience a range of negative emotions (e.g. anxiety, fear,
frustration, boredom, mental distress and, in some species, grief) as well as a range of positive emotions
(e.g. interest, pleasure, happiness, excitement). Primate welfare therefore encompasses the state of
both physical health and psychological wellbeing. Knowledge of the ‘normal state of good health and
psychological wellbeing’ for the species and the individual, taking both aspects into account, is a
prerequisite for the recognition of animals whose welfare is compromised.
There are different types of measure that can be used to evaluate animal welfare and physical health.
(source: Refinements in husbandry, care and common procedures for non-human primates)
http://www.marmosetcare.com/downloads/JointWorkingGponRefinement.pdf Stopped at page 12
(staff training)
Intérêt pour la recherché (avancées qui ont
été rendues possible grâce à cette espèce,
domaine d’utilisation, model pour…)
Nonhuman primates play a unique role in translational science by bridging the gap between basic and
clinical investigations. A comprehensive knowledge of the model system is necessary for appropriate
extrapolation to human beings. Thus, there is a continuum of knowledge between the understanding of
the basic biology, behavior and social organization of nonhuman primate species, and the preclinical
investiga tion of factors that influence nonhuman primate health and what they may tell us about
human health. This continuum stems from the connected- ness of all living beings, but relies heavily on
the phylogenetic closeness of all primates.
Useful in laboratory research because:
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They are widely available (easy to obtain), they have a moderate size, their ability to adapt to
laboratory conditions and the fact that they have been extensively studied.
Macaques have approximately 95% overall genetic coding sequence identity to humans
They are comparable to humans in multiple physiological systems
Cynomolgus and rhesus monkeys are large enough to noninvasively image (e.g. computed
tomography) most systems effectively, yet small enough to house and handle conveniently.
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Much of animal modeling research has utilized young reproductively mature individuals. Disease
processes, however, may be age-dependent. Macaques are long-lived, and thus are effective
models for a number of diseases and conditions that increase in frequency with aging.
animal modeling of human health historically has ignored sex differences, or developed models
in males largely for the sake of convenience, even for studies of diseases that are more common
in women and are known to be influenced by female reproductive system function
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(source: The Unique Value of Primate Models in Translational Research)
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Usefulness for modeling female diseases:
Macaques and apes share with women a true menstrual cycle in which the endometrium is shed
periodically, rather than absorbed as in the estrous cycles of rodents such as rats and mice. The
development of the corpus luteum occurs spontaneously in primates as well as sheep and cows,
whereas it is induced by stimulation of the cervix in other species, including rats and mice The menstrual
cycle of macaques is also similar to that of women in length, variability, and the cyclic pattern of
secretion of sex hormones and gonadotropins Thus, it is not surprising that some disorders of the
reproductive system may be common to macaques and women, including luteal phase defi- ciencies and
hypothalamic amenorrhea These similarities in the reproduc- tive system between nonhuman and
human primates may contribute to similarities in reproductive tissue responses to therapeutic
intervention. For example, in contrast to rodent models, high doses of dietary soy isoflavonoids have
minimal uterotrophic or mammotrophic effects in female cynomolgus monkeys
(source: The Unique Value of Primate Models in Translational Research)
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Usefulness for modeling Cardiovascular Health
Macaques are a well-established model of diet induced CAA [Jokinen et al., 1985]. Atherosclerosis of the
coronary arteries and its complications are the principal pathological processes that result in CHD.
Cynomolgus monkeys are a well-characterized ani- mal model of susceptibility of females to dietinduced atherogenesis. Monkeys imported as adults have little or no atherosclerosis. Atherogenesis
begins when monkeys begin to consume diets containing fat and cholesterol. Ovariectomy results in
extensive CAA [Adams et al., 1985]. If estrogen therapy is begun right after ovariectomy, females are
protected from coronary atherogenesis [Adams et al., 1990;
Adams et al., 1997; Clarkson et al., 2001; Register et al., 2002]. Likewise, the results of large observational studies, such as the Nurse’s Health Study suggest that hormone therapy initiated around the time
of menopause reduces the risk for a major coronary event by about 50% [Stampfer et al., 1985;
Grodstein et al., 2000]. If, however, estrogen therapy in monkeys is not initiated until 2 years after
ovariectomy (approximately equivalent to 6 woman years), there is no beneficial effect on
atherosclerotic plaque size [Clarkson, 2002]. This observation essentially predicted the outcomes of both
the Heart and Estrogen/Progestin Replacement Study and the Women’s Health Initiative, where delayed
initiation of estrogen therapy some 14 to 18 years after menopause was associated with no overall
cardio- vascular benefit [Hulley et al., 1998; Rossouw et al.,2002]. Female cynomolgus monkeys with
poor ovarian function develop extensive CAA like that of ovariectomized females [Adams et al., 1985].
This is not surprising, because females with low progesterone concentrations in the luteal phase also
have low estradiol concentrations in the follicular phase, i.e. they are estrogen-deficient. Thus, ovarian
function, and in particular estrogen, confers protection from CAA in healthy early postmenopausal
women and female cynomolgus macaques. The effects of pre- menopausal ovarian dysfunction on CHD
risk in women are difficult to evaluate, because long-term characterization of hormone levels over the
menstrual cycle is problematic. Nevertheless, women with a history of irregular menses are at increased
risk for CHD [Bertuccio et al., 2007; Solomon et al., 2002]. It is well established that ovarian steroids
modulate inflammatory processes, and this may be an important mechanism underlying sex differences
in cardiovascular risk [Xing et al., 2009].
(source: The Unique Value of Primate Models in Translational Research)
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Musculoskeletal System and Aging
Macaques have been used as models to understand the musculoskeletal system. Skeletal metabolism in
primates differs from that in rodents, as cortical bone in rodents undergoes only limited Haversian
remodeling [Jerome, 2004]. Also unlike primates, rodents continue to grow slowly throughout life.
Macaques are useful models for age-related [Black et al., 2001] and hormone deficiency-induced loss of
bone density [Register et al., 2003] and bone strength [Jerome and Peterson, 2001]. Thus, macaques are
widely used to study osteopenia, osteoporosis [Jerome and Peterson, 2001], and osteoarthritis [Carlson
et al., 1994, 1996]. Furthermore, percentage declines in estimated skeletal muscle mass with age in
macaques are similar to those seen in humans with advancing age, suggesting their utility as a primate
model of sarcopenia [Colman et al., 2005].
Microarray analysis of aging macaque muscle tissue demonstrates selective upregulation of transcripts
involved in inflammation and oxidative stress, and downregulation of genes involved in mitochondrial
electron transport and oxidative phosphorylation [Kayo et al., 2001]. With respect to menopause, a
condition of aging and ovarian senescence in the female, the National Institute of Aging Workshop on
Primate Models of the Menopause concluded that female reproductive aging in the nonhuman primate
is a more appropriate model for the human menopausal process and its connections with menopauserelated health problems than nonprimate species [Bellino and Wise, 2003]. Because of their utility as
models of several systems and disease processes,
nonhuman primates are ideal models for the study of co-morbidities common in aging populations
(source: The Unique Value of Primate Models in Translational Research)
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Central Nervous System and Behavior
The major adaptation that distinguishes primates from all other animals is the expansion and
elaboration of the brain, particularly the cerebral cortex. This adaptation supports sophisticated
cognitive processes, behavioral flexibility, and complex social relationships and organizations, and a
shared similarity in central nervous system organization. The macaque hippocampus, for example, bears
greater resemblance to the human hippocampus than does the rat with regard to nuclear organization,
projection pathways, and innervation patterns.
Likewise, the seroto- nergic system of the monkey shares more similarities with the human than does
the rat with regard to nuclear organization, projection pathways, innervation patterns, axonal
morphologies, and serotonin 1A receptor localization.
Thus, nonhuman primates are optimal models for investigations involving central nervous system
organization and its relation to function. Some notable examples especially relevant to women’s health
include the extensive investigations into the behavioral biology of the mother–infant bond, self-injurious
behavior, anxiety [Bakshi and Kalin, 2000], depression [Shively et al., 2006] cognitive decline, and
Alzheimer’s disease. Ovarian steroid modulation of inflammatory processes also may be an important
influence on neurodegenerative disease progression
(source: The Unique Value of Primate Models in Translational Research)
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Usefulness for modeling Bioenergetics: Obesity and Diabetes
Studies of various aspects of bioenergetics in nonhuman primates, particularly macaques and baboons,
have been very useful in understanding human energy metabolism. These studies have become
increasingly critical as human primates face a gross imbalance in energy intake vs. energy expenditure
that results in excess adipose tissue and a host of pathologies. Primates are preferred models for the
study of whole body obesity [Kemnitz, 1984] as well as some aspects of fat distribution. As in people,
obesity is associated with type 2 diabetes in macaques [Wagner et al.,
2006]. A central fat pattern is associated with carotid and coronary artery atherosclerosis (CAA) in
cynomolgus monkeys and with coronary heart disease (CHD) in people [Shively et al., 1987; Shively et
al., 1990]. Macaques have noninvasively measurable pericardial fat, generally absent in wild-type mice
and rats [Marchington et al., 1989], the secretions of which may directly influence heart and coronary
vasculature function [Baker et al., 2006; Kankaanpaa et al., 2006]. In addition, intra-abdominal
adipocytes from the cynomolgus macaque are similar metabolically to human adipo- cytes [Bousquet
Melou et al., 1995]. Social environ- mental variables affect the distribution of adipose tissue in
macaques as in human primates.
(source: The Unique Value of Primate Models in Translational Research)
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Usefulness for investigating the abnormal development of the human cerebrum:
The cynomolgus monkey (Macaca fascicularis) is a popular laboratory primate belonging to Old World
monkeys, which are the group most closely related to humans except for the apes.
This animal has a highly convoluted surface of the cerebrum forming the sulci and gyri as do humans.
The cynomolgus monkey is a popular laboratory primate frequently used for ‘toxicity testing’ when
rodents and/or rabbits are not pharmacologically relevant species. This primate serves as a useful model
for investigating the abnormal development of the human cerebrum because the primary sulcal pattern
in the cerebrum is comparable with that in humans. In particular, this primate is a worthy model for
human developmental and psychological disorders with the gyrification abnormalities.
(source: Neuroanatomic and magnetic resonance imaging references for normal development of
cerebral sulci of laboratory primate, cynomolgus monkeys (Macaca fascicularis)
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Usefulness for modeling depression:
Animal models are evaluated based on their construct, face, and predictive validities. As such, an ideal
animal model is created through the same etiologic processes as the human disease being modeled
(construct validity), has phenotype similarity to the human disease (face validity), and predicts human
responses to interventions (predictive validity). Developing appropriate animal models of depression has
proven difficult, given the vast heterogeneity in symptomology, causes and course of illness, and
treatment of human depression. There are multiple subtypes within the depression syndrome, and the
symptom diagnosis pool is almost twice that of the number of symptoms that must be present for a
particular diagnosis. In addition, many of the symptoms may be present in one direction or the other,
including increased or decreased appetite, weight, sleep, and motor activity. resulting in patients with a
wide variety of symptom profiles. Reproducing such complex depression symptomology in animal
models is highly challenging, as is assessing the validity of such models when diagnosis is subjective and
so little is known about the pathophysiology of depression.
Nonhuman primates offer the unique opportunity to translate between basic and clinical science.
Macaque species, in particular, have proven advantageous for modeling human disease. Macaques are
small enough to house and handle easily, yet large enough to noninvasively image effectively. They have
95% overall genetic coding sequence identity to humans. and are more similar to humans in multiple
physiological systems than are rodents. Importantly for sex-specific disease processes, female macaques
have a true menstrual cycle like women in which the endometrium is shed, unlike rodents which absorb
the endometrium during the estrous cycle. In macaques, the length and associated hormone
fluctuations of the menstrual cycle are likewise similar to women, thus providing an ideal model for
investigating the relationship between depression and ovarian steroids. Finally, the macaque brain is far
more similar to that of the human in terms of cortex elaboration, nuclear organization, connectivity
patterns, and overall evolutionary conservation of functional areas. Rodent models of depression have
focused on the hippocampus as it is stress responsive. However, cortical areas, particularly the
prefrontal cortex, anterior cingulate, and subgenual cingulate cortex seem to be critically involved in
human depression. These are well represented in the macaque brain, but not present or only
rudimentarily defined in the rodent brain. This neuroanatomical difference limits the translation
between the neurobiology of stress models of depression in rodents and the neurobiology of depression
in primates. (sources: Modeling depression in adult female cynomolgus monkeys (Macaca fascicularis))
Figure 1: A nondepressed monkey (A) compared with a monkey displaying the depressed posture (B).
The nondepressed monkey responds to the photographer, a potential threat, by being alert and
attentive, whereas the monkey displaying depressive behavior is inattentive and in a slumped posture,
with open eyes in a downward gaze. (sources: Modeling depression in adult female cynomolgus
monkeys (Macaca fascicularis))
Other info that might be of interest:
Monkeys are well known globally especially the longtailed macaques.
Macaca fascicularis of Southeast Asia is pervasive but quickly declining in terms of population. They face
many threats including environmental damages and habitat loss with increasing human populations in
both urban and rural sceneries, as well as trade and trapping for pharmaceutical testing, research, and
development (sources: The Dominant Species of Monkeys (Macaca fascicularis) in Northern Region of
Peninsular Malaysia)