Biomedical Engineering Reference
In-Depth Information
nonhuman primate species. By far the majority of
nonhuman primates imported into the USA for research
were macaques, primarily cynomolgus monkeys. Origi-
nating countries (and percent of total imports) included
China (59.8%), Mauritius (17.4%), Vietnam (11.3%),
Cambodia (5.9%), Indonesia (1.2%), and the Philippines
(1.2%).
When acquiring nonhuman primates from foreign
breeding programs, it is useful to be able to review the
facilities' management practices, disease surveillance
records, preventative medicine program, welfare and
enrichment plan, clinical records of animals, and breeding
history of the colony. Breeding history of the colony should
include species and sub-species information on the parents
and offspring. Another important point of review is whether
the colony is closed or receiving expansion/replacement
breeders from an outside source. Programs that employ
even some F
0
breeding should be scrutinized for relative
practices of health quarantine and source and genetic
background evaluation of animals to be introduced into the
colony. This is necessary to limit the risk of contagious
disease and to avoid admixture of differing sub-species into
the breeding colony.
The genetic composition of the parents and offspring
may a have critical role in meeting production goals and in
providing research models suitable to meet particular
research expectations. An understanding of the ancestry of
the parents and some level of genetic information on the
offspring from foreign breeding centers should be achieved
prior to the acquisition of animals for a particular study.
It is well established that species of nonhuman primates
commonly used in research often include subspecies and,
further, that subspecies' differences can affect responses to
a particular study. Variation in test and reference data
between subspecies of nonhuman primates has been
reported. Such differences may include a subspecies'
response in infectious disease research, immunological
expression, physiological and biochemical parameters,
breeding performance, and even behavior. Such findings
have been noted in squirrel monkeys, baboons, rhesus
macaques, and cynomolgus macaques (
Abee, 2000; Wil-
liams-Blangero et al., 2002; Williams-Blangero and Van-
deBerg, 2003; Leuchte et al., 2004; Kawamoto et al., 2007;
Stevison and Kohn 2008; Van Andel et al., 2008
). It should
be noted that morphological inspection alone may be
inadequate for distinguishing subspecies or hybrid animals.
Ideally, to be able to compare data from various research
studies and, further, to manage consistency within control
and test animals, it is preferable to use a single sub-species
that is genetically and physiologically well defined.
Genetic admixture and hybrid animals can impart differ-
ences in response to test articles or procedures, which may
confound results.
Over 19 000 cynomolgus macaques (Macaca
fascicularis) were imported into the USA for use in
biomedical research in fiscal year 2009. These animals
were imported from China, Mauritius, Vietnam, Cambodia,
Indonesia, and the Philippines (
Mullan, 2009
). The genetic
character of all these animals is not consistent across all
sources but varies as a reflection of the wild cynomolgus
(Macaca fascicularis) population from which the parents
were derived. Furthermore, variability may arise from
human influence if animals of different genetic back-
grounds are intermixed in breeding. In general, the captive
breeding colonies of Macaca fascicularis are derived from
one of three populations of free-ranging cynomolgus
monkeys or an admixture of these three populations. These
three sources include cynomolgus derived from Indochina,
Insular Asia (Indonesia, Philippines), and a Mauritian
cynomolgus group (
Stevison and Kohn, 2008
). The last is
a species introduced to the island of Mauritius between 400
and 500 years ago, likely from a relatively very small
founder population originating in Java and/or Sumatra
(
Stanely, 2003; Tosi and Coke, 2007; Blancher et al., 2008;
Stevison and Kohn, 2008
). The insular cynomolgus
macaques split from the continental Indochinese cyn-
omolgus approximately 1 million years ago (
Blancher
et al., 2008
). Cynomolgus macaques of the Philippines
appear to have originated 40 000 to 110 000 years ago, by
natural or human-assisted colonization of an Indonesian
founder population in the Philippines (
Smith et al., 2007;
Blancher et al., 2008
). Genetic evidence indicates that
Indochinese cynomolgus macaques were influenced by
genetic inflow from rhesus macaques, both in the past and
possibly to current times. This event occurs to varying
degrees in geographically distinct intergrade zones of co-
habitation on the mainland (
Leuchte et al., 2004;
Kanthaswamy et al., 2008; Stevison and Kohn, 2008,
2009
). Indochinese cynomolgus breeding animals origi-
nating from widely different locations may display varying
proportions of hybridization, and this may have important
implications on their study use, depending upon the type of
research to be conducted using the offspring. It might be
preferable to keep local populations of Indochinese animals
segregated in breeding systems in order
to produce
a consistent model (
Stevison and Kohn, 2008
).
Particular research goals and methods employing cyn-
omolgus monkeys may dictate a preference relative to the
animal's origin of derivation. In addition to variations
referenced earlier, there are important differences in the
distribution of major histocompatibility complex (MHC)
class I and II alleles. Mauritian cynomolgus monkeys
display a great deal of homogeneity relative to MHC I and
II along with a relatively low genetic variability compared
with Indonesian or Indochinese cynomolgus macaques
(
Krebs et al., 2005; Blancher et al., 2008; Kanthaswamy
et al., 2008
). This characteristic of low variability in MHC
(
Williams-Blangero and VandeBerg,
2003
)
