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ARS Home Midwest Area Ames, Iowa National Animal Disease Center Virus and Prion Research Research Publications at this Location





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Title:   Author  item
                                            LIND, MELISSA - Iowa State Universityitem
                                            Smith, Jodiitem
                                            BRIGGIE, LAUREN - Iowa State Universityitem
                                            WEST GREENLEE, M. HEATHER - Iowa State Universityitem
                                            Greenlee, Justin
  Submitted to: American College of Veterinary Pathologists Meeting
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 9/13/2013
                                    Publication  Date: 11/16/2013
                                    Citation: Lind, M., Smith, J.D., Briggie, L., West Greenlee, M., Greenlee, J.J. 2013. Time-course study of retinal pathology in C57BL/6 mice infected with RML scrapie. American College of Veterinary Pathologists Meeting. Available: http://www.acvp.org/index.php/en/2014-11-07-21-58-13/2013-annual-meeting.Interpretive Summary:
                                Technical Abstract: Prions are proteinaceous pathogens that cause transmissible spongiform encephalopathies (TSEs). These diseases develop slowly as the misfolded and protease-resistant prion protein, PrP**Sc, interacts with the normal cellular form, PrP**C, a cell-surface protein found throughout the nervous system. This interaction causes the normal isoform to refold into PrP**Sc and accumulate within neurons, causing widespread degeneration. Furthermore, PrP**Sc accumulation can be found in numerous other tissues, including the retina. This is known to occur with many TSEs, including scrapie in sheep and goats, and may prove to be valuable for non-invasive, pre-mortem diagnostics. Our study aimed to investigate the course of retinal TSE pathology, using a mouse-adapted strain of the scrapie agent (RML) in C57Bl/6 mice. RML-infected brain homogenate was injected into 51 mice, either intracerebrally or intraperitoneally. Animals were euthanized and tissues collected approximately every 30 days throughout the disease course, then prepared for standard histopathologic and immunohistochemical analysis. Immunohistochemistry was done on retinal tissues using antibodies against PrP (monoclonal antibody 6C2) and Glial Fibrillary Acidic Protein (GFAP), which is upregulated under conditions of retinal stress. Cell counts of the outer nuclear layer were done to quantify retinal degeneration. We found retinal PrP**Sc accumulation, stress, and degeneration are detectable after approximately 80% of the incubation period in mice, for all detection methods and inoculation routes. Albeit, disease severity and progression was slightly lessened for intraperitoneally-inoculated animals. Thus we now have a model for more detailed study of PrP**Sc accumulation and neuronal cell death.


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