NIH Funded Animal Resource Centers at the University of Missouri. Genetically-modified Animals: Powerful tools for biomedical research
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1 NIH Funded Animal Resource Centers at the University of Missouri Genetically-modified Animals: Powerful tools for biomedical research
2 Mice, Rats and Pigs Mutant Mouse Regional Resource Center (MMRRC) Rat Resource and Research Center (RRRC) National Swine Resource and Research Center (NSRRC)
3 Overall Goals Provide valuable animal models to investigators Shift the burden for maintaining and distributing unique animal models from investigators to a National Resource Center Perform research aimed at improving GM animal models
4 Functions Import animals Confirm genotype Cryopreserve germplasm Rederive animals free of infectious pathogens Maintain strains/lines as live animal or cryopreserved material Produce and Distribute animals and cryopreserved materials to biomedical investigators
5 Create Genetically-Modified Swine Genetically-modified swine models are be created for NIH-funded investigators Proposals submitted online and reviewed by NSRRC Advisory Panel No cost to the requesting investigator
6 GeneticallyModified Mice st transgenic mouse st knockout mouse The MMRRC currently holds ~30,000 lines JAX currently holds ~10,000 lines MMRRC:
7 Mice as the predominant species for GM models Short gestation Small, relatively inexpensive to keep Well-defined genetics
8 Genetically Modified Rats Transgenic Rats Targeted Mutations in Rats Transposon/Transposase Zinc Fingers Embryonic Stem Cells
9 Rat models accepted into RRRC Cell/Tissue Markers EGFP (SD, F344, Lewis, Wistar) Alk Phos (F344) LacZ (SD) DS red 2- liver specific (Wistar) Human Transgenes ICAM2-DAF HLA B7 HLA B27 Polycystic Kidney Disease RRRCHan:SPRD-Pkdr1 Behavioral Models Syracuse low & high avoidance Alcohol-Tolerant/ Alcohol-Normal High & Low Alcohol Sensitive Hypertension SS/jrctr & SR/jr Lyon hypertensive, normotensive, hypotensive Hydrocephalus H-Tx/Hcj LEW/Jms Dietary/Obesity DIO & DR F.DIO Miscellaneous Ia osteopetrotic model Spontaneous dwarf rat Belgrade (anemia model) 182 rat models currently available
10 Rats vs. Mice Rats: Advantages Increased size Used extensively for physiologic studies Large Toxicology databases Rats: Disadvantages More expensive Genetics less defined Embryo manipulations more difficult
11 Swine in Biomedical Research GM pigs made using somatic cell nuclear transfer (cloning) Both random and targeted mutations possible Currently 20 GM pig models available from the NSRRC
12 NSRRC Facilities The NSRRC has a separate, new state-ofthe-art facility Facility: houses pigs provides biosecurity to prevent pathogen entry contains laboratory and surgery space
13 Genetic Modifications and Wild Type Animals within the SPF Facility Genetically Modified Models Alpha gal KO and hdaf EGFP (CMV Chicken beta actin promoters) Omega Fatty Acid (Fat-1) Human coagulation factor IX; Human alpha-antitrypsin; von Willibrand factor Miniature Swine NIH miniature pigs (SLA C/C ) Minnesota miniature pigs Wild type Models Ossabaw Yucatan
14 Training the Future Graduate students from the schools of Medicine, Veterinary Medicine and Engineering Veterinarians from a nationally recognized Comparative Medicine Program (CMP) Trains veterinarian in comparative medicine research and the specialty of laboratory animal medicine Veterinary students in the Veterinary Research Scholars Program (VRSP) Provides veterinary students opportunity to explore research career opportunities Strong collaborations with Kansas State University Future trainees in the Institute for Clinical and Translational Science Integration of research and clinical training for medical students
15 Do you worry that your animal model may be lost due to disease or genetic instability? Is the demand for your animal model by other investigators more than you can accommodate? The NIH-funded Animal Resource Centers for mice, rats & swine can help! The Resource Centers provide the following services: Cryopreserve and store models to prevent loss Rederive models to eliminate pathogens Distribute valuable models to investigators Provide health and genetic monitoring Mutant Mouse Regional Resource Centers Rat Resource & Research Center National Swine Resource & Resource Center
16 Acknowledgements Principal Investigators Lela Riley Randy Prather John Critser Managers MMRRC and RRRC Beth Bauer NSRRC Eric Walters NIH NCRR, NHLBI, NIAID
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