Comparative Medicine Vol 53, No 4 Copyright 2003 August 2003 by the American Association for Laboratory Animal Science Pages 383-392 Overview Marmoset Models Commonly Used in Biomedical Research Keith Mansfield, DVM The common marmoset (Callithrix jacchus ) is a small, nonendangered New World primate that is native to Brazil and has been used extensively in biomedical research. Historically the common marmoset has been used in neuro- science, reproductive biology, infectious disease, and behavioral research. Recently, the species has been used in- creasingly in drug development and safety assessment. Advantages relate to size, cost, husbandry, and biosafety issues as well as unique physiologic differences that may be used in model development. Availability and ease of breeding in captivity suggest that they may represent an alternative species to more traditional nonhuman pri- mates. The marmoset models commonly used in biomedical research are presented, with emphasis on those that may provide an alternative to traditional nonhuman primate species. In contrast to many other laboratory animal species, use of nonhuman primate species. nonhuman primates has increased in recent years and there Common marmosets represent an attractive alternative non- currently exists a substantial shortage of such animals for use human primate species for a variety of reasons. These small in biomedical research. The national supply of macaque mon- hardy animals breed well in captivity, with reproductive effi- keys has been unable to meet the current or projected demands ciency that may exceed 150% (number of live born per year/ of the research community. Although efforts are underway to number of breeding females). Furthermore, sexual maturity is increase domestic production and to identify alternative foreign reached by 18 months of age, allowing rapid expansion of exist- sources, this will unlikely alter short-term availability. Despite ing colonies. The small relative size of the common marmoset, these ongoing efforts, the shortage of well defined research ani- compared with that of macaque species, may represent another mals likely will negatively impact national biomedical and de- potential advantage. This smaller size translates into lower cag- fense research initiatives for the foreseeable future. In addition ing and feeding costs and reduced floor space requirements. to increasing production of rhesus macaques, one solution to Smaller size facilitates social housing of common marmosets this shortage is to provide alternative primate species that may and implementation of environmental enrichment programs. be used by investigators in their research programs. The com- The marmoset is less destructive to its environment than are mon marmoset (Callithrix jacchus) is one such species, and has larger nonhuman primates, which makes possible provision of a a number of distinct advantages, compared with those of other more complex and enriching environment. In drug development, larger Old World primates. reduced body mass may substantially decrease compound syn- The common marmoset is a small New World primate that is thesis costs and time requirements. This coupled with lower pur- native to eastern Brazil and has been used extensively in biomedi- chase price of common marmosets, compared with macaques, cal research models in North America and Europe. New World pri- may translate into substantial cost savings when performing mates (platyrrhines) represent a diverse group of animals equivalent studies. encompassing two families (the Cebidae and Callitrichidae), and Enhanced biosafety represents an additional benefit. Marmo- at least 76 distinct species. Separation from Old World primates sets may carry infective agents, such as Giardia, Cryptosporidium, occurred approximately 26 to 27 million years ago, and this and Strongyloides spp., as well as other zoonotic disease organ- early separation coupled with adaptations to the neotropical isms; however, they do not spontaneously harbor herpes B virus environment has resulted in a number of distinct differences (Cercopithecine herpesvirus 1). Although universal precautions from Old World primates (catarrhines). The laboratory animal should be followed when handling any nonhuman primates, scientist must appreciate these substantial differences in physi- this may alleviate some biosafety concerns at facilities that no ology, behavior, dietary requirements, and disease susceptibili- longer accept animals that are seropositive for this agent. ties when using marmosets in pursuit of their research goals. A number of unique physiologic differences between Old Such differences may also present unique opportunities in World and New World primates have been used in the develop- model development that are not available in more traditional ment of novel models. Examples include anatomic differences in placentation, which leads to bone marrow chimerism of twins. Received: 4/21/03. Revision requested: 6/02/03. Accepted: 7/07/03. Twins may be used in adoptive transfer experiments to examine New England Primate Research Center, Harvard Medical School, One Pine Hill components of the cellular immune responses to a variety of Drive, Southborough, Massachusetts, 01772. antigens and in disease pathogenesis (48). Similar experiments 383 Vol 53, No 4 Comparative Medicine August 2003 are currently difficult or impossible to perform in Old World pri- Table 1. Examples of infectious disease models involving the common mates. Limited diversity at both major histocompatibility com- marmoset (Callithrix jacchus) plex (MHC) class-I and -II loci has been identified in tamarins Agent Animal model Reference and marmosets, and may be responsible for differences in dis- Viral ease susceptibilities that are exploited in infectious disease Herpesvirus ateles Acute oncogenesis (3) studies (5). Finally, unique features of marmoset biology have Herpes simplex virus Vector safety assessment (64) Herpesvirus saimiri Acute oncogenesis (123) facilitated examination of the behavioral regulation of repro- Epstein Barr virus Viral persistence (32) ductive performance. Hepatitis A virus Acute hepatitis (94) Although there are appreciable advantages to the use of mar- GB virus B Acute hepatitis (25) Measles virus Pathogenesis (77) mosets in the vivarium, there are also potential disadvantages Junin virus Hemorrhagic fever (6) that must be overcome. Size and cost are relative, and though Parasitic the purchase price and cost of housing a common marmoset are Brugia malayi Filariasis (36) less than those of a rhesus macaque, they are substantially Plasmodium sp. Malaria (92) more than those for most rodent or other non-rodent species. Bacterial Similarly, although their size may be of benefit in some studies, Mycoplasma genitalium Urogenital infection (117) this smaller size may make it difficult or impossible to perform Legionella pneumophila Legionnaire’s disease (14, 15) certain procedures or techniques. For example, size may limit Chlamydia trachomatis (68, 69) the type and volume of blood samples that may be obtained. In Chronic periodontal disease (4, 82) general, maximal blood draw is one percent of body weight or Other three to four milliliters once every two to three weeks. Marmo- BSE/scrapie Prion disease (7) sets may also require specialized husbandry and veterinary BSE = Bovine spongiform encephalopathy. care, which may not be available at all facilities. Finally, one of the reasons that rhesus macaques are attractive as a model is complementary strands of DNA. Recently, the Affymetrix the critical mass of investigators using this species. Thus, tools GeneChip (Affymetrix, Santa Clara, Calif.) has been validated in initially developed in one model may be applied to others, and several species of nonhuman primates, including common mar- synergies are established when divergent groups use similar mosets, and has been used to investigate gene expression in species. Since there are currently fewer investigators using brain tissue (85). marmosets, this synergy is not as well advanced. Research Areas Research Tools Historically the common marmoset has been used in neuro- The laboratory animal scientist and veterinary staff often science, reproductive biology, infectious disease, and behavioral play a key role in assisting investigators in the selection of ap- research. Recently the species has increasingly been used in propriate animal models. The availability of research tools is a drug development and safety assessment. critical issue when evaluating species choice in model develop- ment. Although there are clearly not as many research tools Infectious Diseases available for marmosets as there are for macaque species, re- Historically, common marmosets have been used extensively in sources have now been developed in a number of key areas. Ex- infectious disease research due in large part to their unique sus- amples include demographic databases (115, 116, 127) as well ceptibility to a number of important human infective agents. Re- as specialized techniques, such as remote telemetry, stereotactic search programs have been established to examine viral, bacterial, neuroanatomic localization, and multi-electrode implantation and parasitic agents. In particular, marmosets are susceptible to a (19, 35, 52, 81). variety of herpesvirus agents, including gammaherpesviruses, Immunohistochemical analysis is a critical tool that can be such as Epstein Barr virus (EBV) and Herpesvirus saimiri (HVS), used to interpret morphologic changes in tissue