Care, Use, and Welfare of Marmosets as Animal Models for Gene Editing-Based Biomedical Research Proceedings of a Workshop (2019) / Chapter Skim
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4 Current Research Applications
4 Current Research Applications
Pages 23-40
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Investigators at NINDS have, since 1997, been developing marmoset models for experimental autoimmune encephalomyelitis (EAE) , a disease that in marmosets approximates the key pathological features of the human disease multiple sclerosis (MS)
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In marmosets, the development of brain lesions closely resembles the process in humans and brain imaging enables researchers to track lesion development and the integrity of the blood brain barrier as the disease progresses. The marmoset EAE model shows different characteristics compared to EAE models in mice or macaques.
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. Marmoset brains can be imaged while the animals are awake or sedated.
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FIGURE 4-3 Schematic of cradle setup for performing functional MRI (fMRI) on conscious awake marmosets.
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The few animals that showed agitation during MRI training were removed from the study and the training was discontinued. Imaging disease models and healthy animals with sophisticated equipment reveals detailed networks of blood vessels in the brain, myelination in the cortex, contrasts between gray and white matter, contrasts between the brain and cerebrospinal fluids, and the brain's overall water content, data points that provide valuable insights about the progression of EAE-induced lesions in the marmoset brain (Absinta et al.
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To overcome this problem, BRPC researchers developed a slow-progressing MPTP Parkinson's model (Philippens 2017)
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This example underscores the importance of selecting the right animal model for the research questions being addressed, the participant noted. Using Marmosets to Study Sleep and Stress Langermans noted that BRPC researchers have recently begun using biomarkers to validate their findings about early-stage neurological disease.
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During the discussion, participants noted how, even though marmosets interact socially with each other in ways that are very different from human interactions, researchers have identified behaviors relevant to human conditions that affect social interaction, like autism spectrum disorder. For example, one participant noted that altering certain neurons in marmosets can lead to changes in eye movements and social interactions, suggesting marmosets altered in this way could offer a model for researching autism or other disorders.
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Marmosets as Models for Aging Researchers are comparing aging across species to advance translational animal research and bridge the gap between geriatricians (i.e., clinical scientists who study human aging processes through longitudinal or epidemiological studies) and gerontologists, who study basic science to uncover different pathways that are associated with aging, such as telomere damage or cell loss.
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Homeostatic balance is measured via blood pressure and microbiome assessment. Aging marmosets have higher diastolic and mean arterial pressure measurements, but other blood pressure measures remain stable.
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Ross and her team determined that low doses of rapamycin do not affect marmoset metabolic function, indicating that it is unlikely to cause diabetes in otherwise healthy humans or animals (Ross et al.
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Lassa Virus Lassa virus causes fatal hemorrhagic fever and is endemic to West African rodents. Infected marmosets react very similarly to humans, showing severe morbidity 15 and 20 days post-infection and similar histopathological findings.
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Patterson and her colleagues have collaborated with other researchers to develop an Ebola vaccine using a marmoset model. GB Virus B GBV-B resembles hepatitis C, a disease for which chimpanzees are the only available animal model.
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when testing for viruses or antibodies. GENE EDITING AND TRANSGENIC ANIMALS Erika Sasaki, the director of marmoset research for the Central Institute for Experimental Animals (CIEA)
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, which are not available for most mammals, including marmosets. Emerging Gene Editing Techniques To make knockout marmoset models, CIEA scientists explored several recent genome editing techniques.
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She reminded the audience that pre-evaluation of the genome editing tools is important and that target gene knock down could be another method to avoid embryonic lethality. DISCUSSION In the discussion, an attendee pointed out that the use of transgenic technologies raises the prospect that genetically modified animals could potentially end up in the wild where they could interbreed with wild populations.
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2015. Metabolic consequences of long-term rapamy cin exposure on common marmoset monkeys (Callithrix jacchus)
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2018. Experimental Zika virus infection in the pregnant common marmoset induces spontaneous fetal loss and neurodevelop mental abnormalities.
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