The common marmoset as a novel animal model system for biomedical and neuroscience research applications

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Summary

The common marmoset (Callithrix jacchus), a small New World primate, has been attracting much attention in the research field of biomedical science and neuroscience, based on its (i) cross-reactivity with human cytokines or hormones, (ii) comparative ease in handling due to its small size, (iii) high reproductive efficiency, (iv) establishment of basic research tools, and (v) advantages of its unique behavioral and cognitive characters. Various neurological disease models have been developed in the common marmoset, including Parkinson's disease, Huntington's disease, Alzheimer's disease, stroke, multiple sclerosis and spinal cord injury. We recently developed transgenic common marmoset with germline transmission, which is expected to provide a new animal model for the study of human diseases. In this review, we summarize the recent progress of biomedical research and neuroscience using common marmoset as an excellent model system.

Introduction

The common marmoset (Callithrix jacchus) is a small New World primate that, because of its size, availability, and unique biological characteristics,1 has attracted considerable attention as a potentially useful animal model in fields such as neuroscience, stem cell research, drug toxicology, immunity and autoimmune diseases, reproductive biology and regenerative medicine.2 The common marmoset is originally from the Amazon basin of Brazil. Separation of the New World primates and Old World primates occurred about 35 million years ago and this early separation, coupled with adaptations to the neotropical environment, produced a number of distinct differences in physiology and disease susceptibility between Old and New World primates. As a result of this split, some of the traits of the common marmoset are more similar to humans than macaques. The advantages of the common marmoset as an animal model for biomedical research are severalfold:

  • 1.

    Marmoset cells exhibit cross-reactivity with human cytokines or hormones. The common marmoset has a similar disease susceptibility profile to humans, making it a suitable model system for toxicology screening, drug development and infectious disease research.1, 2, 3 The teratogenic effects of some compounds have been shown to differ significantly between rodent and primate species. For example, whereas rodents are not sensitive to the teratogenic action of thalidomide analogue, the common marmoset is sensitive to this compound.4, 5, 6 Anatomical similarities in placentation between humans and marmosets could be responsible for these observations. Furthermore, common marmosets have been used extensively in infectious disease research,1 as a model of hepatitis A virus infection,7 malaria,8 and prion diseases9 due to their unique sensitivity to these human infectious agents.

  • 2.

    Common marmosets can be handled with comparative ease. The body height and weight of the adult common marmoset is 20–30 cm and 350–400 g, respectively, which translates into lower caging and feeding costs and reduced floor space requirements.1 Because of these advantages, the common marmoset has been used as a versatile model system of spinal cord injury10 for a wide range of preclinical testing.

  • 3.

    Common marmosets have high reproductive efficiency with an early onset of puberty (around 1.5 years old), relatively large litter sizes (two to three per delivery), and a relatively short gestation period and delivery interval (145–148 days and 154–157 days, respectively); thus, they have a relatively large number of deliveries (20–30 during the course of their lifespan) and offspring (four to seven per year, or 40–80 during their lifespan). Compared to a macaque, for example, from which one could obtain three pups in 3 years, one could reasonably expect to obtain 14 marmoset pups over the same period. The pups reach sexual maturation at around 18 months, which translates in theory into 54 pups over 3 years. Such remarkable reproductive efficiency in marmosets provides a strong advantage in terms of the development of transgenic animals.

  • 4.

    Important basic research tools for marmosets have been developed. For example, genome research is ongoing, and various magnetic resonance imaging (MRI) techniques11, 12, 13 and an MRI atlas are now available. There has also been remarkable progress in the development of transgenic techniques14 and tools related to embryonic stem cells (ES cells)15 and induced pluripotent stem cells (iPS cells)16 for marmosets.

In the field of neuroscience, there has been increasing interest in the common marmoset as an animal model for the following reasons: (i) there is greater similarity between marmoset and human than between rodent and human in terms of developmental processes and brain anatomy and function17; (ii) adult neurogenesis occurs in marmoset18, 19, 20; (iii) there are similarities in social behaviors between marmoset and human and strong relationships between parents and offspring21; (iv) marmoset has a unique vocal form of social communication22, 23; (v) marmoset models are available for neurological diseases and preclinical models (described later); (vi) some higher cognitive tasks in marmosets are equivalent to those of macaques.24

In this review, recent developments in neuroscience and medical science using the common marmoset as a model system, including the development of transgenic techniques, are summarized.

Section snippets

Neurological disease models (including a model of spinal cord injury)

Common marmoset models of various neurological diseases have been developed, including Parkinson's disease,25, 26 Huntington's disease,27 Alzheimer's disease caused by spontaneous amyloid deposition28 or experimentally induced,29 stroke,30 multiple sclerosis (experimental allergic encephalitis model)31 and spinal cord injury (SCI).10 The greater similarity between marmoset and human compared with rodent in terms of anatomical structure and function of the brain supports the use of the common

Magnetic resonance imaging

Various MRI techniques for common marmoset have been developed (Fig. 1), including diffusion tensor tractography (DTT) for in-vivo tracing of axonal fibers of the spinal cord11 and visual system,12 voxel based morphometric (VBM) analysis13 and myelin mapping (K. Fujiyoshi et al., unpublished data).

Conventional MRI shows white matter as a homogeneous tissue, even though it actually contains a complex array of specifically oriented nerve fibers. Methods to visualize these pathways in white matter

Pluripotent stem cells

There are several important applications of non-human pluripotent stem cells (including ES cells and iPS cells), including: (i) studies of early embryonic development and specification of the three germ layers, (ii) preclinical studies of regenerative medicine, and (iii) transgenic techniques. Our collaborative team has generated both ES cells15 and iPS cells16 for these purposes. In 1996, Thomson et al.48 established common marmoset ES cell lines, which to this day are considered powerful

Transgenic techniques and neurological disease models

The creation of transgenic mice was a major contribution to the field of life science research, particularly efforts to clarify the genetic functions and molecular mechanisms underlying various pathological conditions. However, in many cases, research results obtained in mice cannot be directly applied to humans because of the many physiological, anatomical and histological differences between mice and humans, which are evolutionarily distinct. For this reason, there is a need for more research

Future perspectives

The successful creation of transgenic marmosets provides a new animal model for the study of human disease that has the singular advantage of a close genetic relationship with humans.14 The use of transgenic marmosets has the potential to contribute significantly to the development of therapeutic methods for addressing currently intractable neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis, as well as mental disorders such as schizophrenia and autism.

Conflict of interest statement

None declared.

Funding sources

This work was supported by grants from the “Highly creative animal model development for brain sciences” study carried out under the Strategic Research Program for Brain Sciences by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and from the “Funding Program for World-leading Innovative R&D on Science and Technology” to H.O.

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