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Comparative Medicine Resources OFFICE OF RESEARCH INFRASTRUCTURE PROGRAMS FACT SHEET COMPARATIVE SPRING 2017 MEDICINE ORIP MISSION The Office of Research Infrastructure Programs RESOURCES (ORIP) advances the NIH mission by supporting research infrastructure and research-related resources programs, and coordinating NIH’s science education https://orip.nih.gov/comparative-medicine efforts. ORIP’s programs support biomedical researchers with the infrastructure and research- related resources they require to advance medical research and continue improving human health. OVERVIEW Comparative Medicine plays an essential role in biomedical discovery by enabling scientists to better understand, diagnose, prevent, and treat human diseases. Often serving as a bridge between basic science and human medicine, animal models1 have enabled numerous major medical advances—safe and effective vaccines, including Hepatitis A and B immunizations; improved cancer treatments; blood transfusions; organ transplantation; bypass surgery; and joint replacement. Animal • Support phenotypic and genetic characterization models are actively being used to understand the causes of animal models and the development of new and of, and develop therapies for, almost all human conditions, improved long-term storage of animal germ plasm. including cancer, cardiovascular disease, diabetes, obesity, and neurodegenerative and infectious disease. • Support studies aimed at improving the welfare and husbandry of laboratory animals. • The Division of Comparative Medicine (DCM), within the Office of Research Infrastructure Programs (ORIP), • Enable career development and translational research Division of Program Coordination, Planning, and training for veterinary students and veterinarians as well Strategic Initiatives (DCPCSI), National Institutes of as for post-doctoral investigators who use laboratory Health Office of the Director (NIH/OD), works to: animals. • Ensure that NIH-supported researchers have access to, • Increase public-private partnership opportunities with and facilities for, animal models critical to research. small businesses. USING ANIMAL MODELS TO ADVANCE TRANSLATIONAL RESEARCH DCM supports a broad range of translational research of California at Davis, University of Missouri, University of projects and resources that develop and enhance access North Carolina at Chapel Hill, and The Jackson Laboratory) to animal models, including rodents, aquatic models, and an Informatics, Coordination, and Service Center nonhuman primates, invertebrates, and others. Visit the (University of California at Davis) collectively strives to DCM webpages for a complete list of resources. preserve, protect, ensure quality control, and provide these models for the benefit of research scientists and Rodents investigators across the nation and the globe. Each Rodents are the most frequently used species in biomedical center provides services on a fee-for-service basis, such research. Mice, for example, have much in common with as cryopreservation of mouse embryos and gametes, people in terms of genetics, development, physiology, rederivation of living mice from cryopreserved embryos behavior, and disease susceptibility. To ensure that mice and and sperm, quality control testing for mouse pathogens, other genetically altered rodents with defined mutant genes mutagenesis and embryonic stem cell isolation, and cloning, are accessible to the research community, DCM supports phenotyping, and genotyping services. several rodent resource programs to sustain special animal colonies and genetic stocks. • The Special Mouse Strains Resource (SMSR) is a resource of special strains of mice that are valuable Mutant Mouse Resource and Research Centers (MMRRCs) tools for genetic analysis of complex diseases at Jackson maintain and distribute mutant mouse strains for use Laboratory. They include panels of recombinant inbred in biomedical research. The centers collect transgenic, (RI) and chromosome substitution (CS) strains. The knockout, and other kinds of induced mutant mouse SMSR imports, cryopreserves, and distributes RI and CS lines and distribute them for a small fee to requesting strain panels that are vital to discovery of quantitative researchers. A national network of four MMRRCs (University 1 The National Institutes of Health considers very carefully the use of animals in research. Long-standing policies require careful review of all biomedical research studies that propose the use of animals. Research projects using animals are funded only if justified by the potential impact on human health. See the latest news, policies, education and training materials, and information about animals in research at the NIH Office of Extramural Research website, OER Animals in Research. All animal laboratory facilities funded by DCM are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. trait loci and, ultimately, the genes responsible for specific pathogen-free (SPF) mice of different genetic complex diseases. These special strains of mice are backgrounds, to explore the functional alterations of important tools for genetic analysis of such diseases as normal vs. dysbiotic bacterial communities in murine diabetes, cardiovascular disease, obesity, autoimmune models and human diseases, and to define the disease, and cancer. functional relevance of bacterial genes. The microbiota can be precisely manipulated by colonizing germ-free • Several resources supported by DCM are developing rodents with single or multiple resident or pathogenic mouse strains for improved humanized mouse models. bacterial or viral or fungal species using isogenic wild A humanized mouse is one that carries functioning type or genetically-engineered bacterial strains. human genes, cells, tissues, and/or organs. Such animals are commonly used as small animal models in • The Adult Mesenchymal Stem/Stromal Cell Resource biological and medical research for human therapeutics. provides fully characterized rodent bone marrow- The Center for Humanized Mice offers environmentally, derived cells referred to as mesenchymal stem cells genetically, and xenotransplantation-engineered mouse or mesenchymal stromal cells (MSCs). These cells are models for translational studies and drug discovery; isolated from bone marrow, expanded, tested under activities focus on improved animal models to study standardized protocols, and made available to the human immunity, human-specific infections, vaccines, scientific research community. The cells can serve as and human-specific drug interactions. Stem cells and a standard against which other sources of MSCs are regenerative medicine are the focus of a number of compared or as a source of cells for specific research other DCM projects. applications • The Rat Resource and Research Center (RRRC) distributes Aquatic Models high-quality, well-characterized inbred, hybrid, and mutant Aquatic animals, including zebrafish, salamander, frogs, rat strains to investigators. This center selects and imports and marine slugs, can serve as models for studying human rat strains and stocks that are important to biomedical development, behavior, and disease. Because of their research, achieves pathogen-free status, cryopreserves short reproductive cycles and transparent eggs, they offer gametes and embryos, and performs genotyping and researchers the ability to easily observe them as they develop. infectious disease monitoring to assure the quality of rats. Germline-competent rat embryonic stem cell lines, Using these model organisms, researchers can identify including several on different genetic backgrounds and potential functions of specific genes; this allows them to several containing EGFP, are also available. better understand the underlying basis of genetic disorders in people. Aquatic models have been important in studies • The National Gnotobiotic Rodent Resource Center of gene function, protein interactions, and pathological provides a resource for broadly based NIH- processes related to humans. DCM supports aquatic funded investigators to examine physiologic and models of research through funding the development and pathophysiologic differences in germ-free (sterile) maintenance of critical genetic stocks, biological materials, vs. gnotobiotic (known life, selectively colonized) vs. and online information. Through the National Swine Resource and Research Center, DCM ensures that valuable swine models are available to the biomedical research community. The repository creates new genetically modified pig lines and performs research aimed at improving swine models. The Zebrafish International Resource is a central repository DCM also supports the development and use of for wild-type and mutant strains of zebrafish, and it serves as invertebrate comparative models as a complement to a resource for zebrafish research information and biological rodent, fish, and NHP models. Simpler species, including materials. The resource maintains healthy stocks of zebrafish Drosophila (fruit flies) and C. elegans (roundworms), and frozen sperm as well as appropriate strains of wild-type are genetically well characterized and can be readily fish for distribution to the research community. manipulated genetically. Additional simple models supported by DCM include in Strongylocentrotus Nonhuman Primates purpuratus (sea urchins), Euprymna scolopes (squids) and The close molecular, immunological, molecular, metabolic, Tetrahymena (cilia). Because these models are relatively reproductive, and neurological
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