The Historical use of Callitrichines in Biomedical Research and Current Trends. Suzette D. Tardif, PhD

Size: px

Start display at page:

Download "The Historical use of Callitrichines in Biomedical Research and Current Trends. Suzette D. Tardif, PhD"

Kristin Daniel
5 years ago
Views:

1 The Historical use of Callitrichines in Biomedical Research and Current Trends Suzette D. Tardif, PhD

2 What are callitrichines? History of use Impediments to growth in use Recent drivers of use and how they differ from historic use Goals moving forward

Callitrichidae Now Subfamily Callitrichinae Previously all called marmosets Now

3 What s in a name? Saguinus oedipus Cotton-top marmoset Cotton-top tamarin Previously Family Callitrichidae Now Subfamily Callitrichinae Previously all called marmosets Now differentiated into marmosets and tamarins Cotton-eared marmoset Common marmoset Hapale jacchus Callithrix jacchus S. fuscicollis White lipped marmoset Saddle-backed tamarin

4 Derived Characteristics of Callitrichines Small size Litters not singleton births Hematopoietic chimerism Absence of 3 rd molar Loss of molar hypocone Claws & apical pads Cooperative infant care? Female reproductive suppression

5 Harris, Tardif, et al., PNAS, 2014 Proposed Evolutionary Relationships of Derived Traits

Historical Use While kept in captivity for centuries, biomedical use dates back to ~ 1960 Marmosets were chosen for trial as laboratory primates because they seemed to fulfill some of the

6 Historical Use While kept in captivity for centuries, biomedical use dates back to ~ 1960 Marmosets were chosen for trial as laboratory primates because they seemed to fulfill some of the requirements which would qualify any primate species as useful for biological research. Animals were available in large numbers and at low cost. The small size and demands on animal husbandry made it likely that animals could be kept under standard laboratory conditions. Deinhardt, et al., Lab Anim Care, 1967

7 Use in US and Europe fed primarily by importation through the 1960 s and into the 1970 s Primarily tamarins Primarily marmosets

8 Species at the Marmoset Research Center, Oak Ridge Associated Universities, early 1970 s Saguinus nigricollis S. labiatus Callithrix jacchus S. oedipus S. fuscicollis S. mystax S. midas Cebuella pygmaea

9 Species at the Marmoset Research Center, Oak Ridge Associated Universities, early 1980 s Saguinus nigricollis S. labiatus Callithrix jacchus S. oedipus S. fuscicollis S. mystax S. midas Cebuella pygmaea

10 Infectious disease Radiation Biology/Transplant Biology Viral oncology Hepatitis GBV-B Chimerism/Immunology Ethology Teratology Atherosclerosis Neuroscience Induced Parkinson s Obesity Met syndrome Reproduction Assisted Repro Tech Anti-renin therapy Genomics Stem cells Gene Therapy Transgenics Biodefense EAE-MS model Aging

11 Impediments to Growth in Use in the US Why aren t they readily available and cheap anymore? Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) includes ALL primates, not just those that are endangered Pre-CITES: Estimates of > 200,000 primates exported from Central and South America in the 1950 s-1960 s (Mittermeier, et al., 1989, J Hum Evol) Biomedical exports of > 20,000 described as contributing to endangerment of the cotton-top tamarin (S. oedipus) Post-CITES Estimates of total South American primate exports of < 5,000 between 1977 and 2013 (Fialho, et al., 2016, Primate Cons, 2016)

12 Impediments to Growth in Use in the US Why aren t they readily available and cheap anymore? Why aren t they small macaques? Or large mice? Sometimes framed as the fragility question. Lack of basic understanding of housing/social requirements Difficult dietary transitions we still have no standardized captive diet Marmoset Wasting Syndrome likely a composite of different conditions/etiologies Nutrition camp protein deficiency, vitamin E deficiency, vitamin D deficiency, gluten sensitivity Stress camp Infectious disease camp E coli, Campylobacter, Trichospirura leptostoma Breeding issues (more difficulties with tamarins) Poor parenting performance Handling of supernumerary infants

13 Impediments to Growth in Use in the US Why aren t they readily available and cheap anymore? Why aren t they small macaques? Or large mice? Sometimes framed as the fragility question. Why don t these reagents work? Issues with failures in antibody-based reagents

Neuroscience Recent Drivers of Increased Use Visual Systems, Auditory Systems, Cognitive Function, Wiring/Connectivity Benefits of the marmoset Lissencephalic

14 Neuroscience Recent Drivers of Increased Use Visual Systems, Auditory Systems, Cognitive Function, Wiring/Connectivity Benefits of the marmoset Lissencephalic cortex Ease of social housing in conventional vivariums Will drive toward many, relatively small colonies (20-60) maintained at primarily academic institutions

Recent Drivers of Increased Use Neuroscience Gene Editing/Transgenics Benefits of the marmoset Ability to gestate up to 4 embryos per pregnancy Production of up to 2 pregnancies per year Maturation

15 Recent Drivers of Increased Use Neuroscience Gene Editing/Transgenics Benefits of the marmoset Ability to gestate up to 4 embryos per pregnancy Production of up to 2 pregnancies per year Maturation at 18 months Will drive toward a relatively small number of large colonies ( ) for transgenic production a small number of very large colonies (1,000) for line maintenance and characterization Sasaki, et al., 2009 Nature

16 Goals moving Forward Establish a stable platform of evidence-based standards of captive management Develop the tools (molecular, genomic, imaging) needed to support the marmoset as a model Develop plans for transgenic development that are focused and supportable from both a scientific and welfare standpoint (e.g. clearinghouses)

Acknowledgements: Conrad Richter, VMD, Marmoset Research Center, ORAU Arlan Richardson, PhD, Barshop Institute for Longevity & Aging Studies Nicholas Musi, MD, Barshop Institute for Longevity & Aging

17 Acknowledgements: Conrad Richter, VMD, Marmoset Research Center, ORAU Arlan Richardson, PhD, Barshop Institute for Longevity & Aging Studies Nicholas Musi, MD, Barshop Institute for Longevity & Aging Studies Robert Lanford, PhD, Southwest National Primate Research Center Corinna Ross, PhD Donna Layne-Colon, BA R01-RR02022; R01-DK077639; R24-RR023344; R24-OD P51 OD011133; P30AG Fitzgerald, A Rearing marmosets in captivity. J. Mammalogy, 16:181-88

CARE, USE AND WELFARE OF MARMOSETS AS ANIMAL MODELS FOR GENE EDITING-BASED BIOMEDICAL RESEARCH

A Roundtable on Science and Welfare in Laboratory Animal Use Workshop CARE, USE AND WELFARE OF MARMOSETS AS ANIMAL MODELS FOR GENE EDITING-BASED BIOMEDICAL RESEARCH October 22-23, 2018 Keck Center 500