Bioassays of prions and replication of prions to high titers must still be performed in animals. Generally, laboratory rodents can be used. Transgenic mice expressing foreign and mutant PrP genes have revolutionized prion research. A highly efficient Animal Core is required for the studies described in this application. The specialized personnel, facilities, techniques and procedures required for prion research have been developed over the past 15 hears at UCSF. The Animal Core is directed by Dr. Marilyn Torchia, a veterinarian with many years of experience in the care of laboratory animals. Transgenic mice will be constructed, produced and evaluated by the Animal Core. Some transgenic mice will be analyzed for scrapie incubation times after inoculation with prions, while others which are uninoculated will be observed for the onset of spontaneous disease. Besides measuring incubation times, end point titrations of prions will be measured for a small number of selected samples. Prions will be replicated to high titers in Syrian hamsters. After these hamsters. After these hamsters develop clinical signs of neurologic dysfunction, they will be sacrificed and their brains removed. From frozen hamster brains, prions will be purified as described in the Scientific Core. To insure accurate record keeping and to facilitate all phases of the Animal Core operations, mice are tattooed with a number which corresponds to a bar-code on the cage card. Bar-code readers are used to enter all data on the status of each animal. Data is then downloaded to a """"""""PC"""""""" computer and analyzed using a modified database program. We anticipate that our computerized animal care management system will become even more important as transgenic mice are transgenic mice are mated with mice carrying ablated PrP alleles. Because of the prolonged incubation times in prion diseases, many experiments must be done in parallel. Economic and physical limitations on the Animal Core necessitate careful planning and frequent reevaluation of priorities. In order to maximize the number of animals that are evaluated, cost containment and reduction are constant objectives. The specialized capabilities and services of the Animal Core described here are crucial for all phases of prion research.
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