Submitted to: Journal of Veterinary Diagnostic Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/5/2004
Publication Date: 11/1/2004
Citation: Caplazi, P., O'Rourke, K.I., Wolf, C., Shaw, D., Baszler, T. 2004. Biology of PrP-Sc accumulation in two naturally scrapie-infected sheep flocks. Journal of Veterinary Diagnostic Investigation. 16(6):489-496.
Interpretive Summary: Scrapie is a fatal neurodegenerative disease of sheep, associated with deposits of an abnormally folded protein (PrP-Sc) in the brain, reproductive tract, and lymphoid system of infected sheep. This papers adds to previous data of natural sheep scrapie. The tissue and cellular location of PrP-Sc in the infected sheep of these flocks was consistent with that observed in European and British flocks. Clinical disease was always associated with PrP-Sc in brain. Preclinical scrapie was characterized by accumulation of PrP-Sc in lymphoid tissue, without evidence of the protein in the brain. PrP-Sc was found in trophoblast (fetal) cells in pregnant ewes, although not in the uterine tissues of the ewe. Examination of the cellular location and processing of PrP-Sc will be useful in refining highly specific and sensitive diagnostic tests.
Technical Abstract: PrP-Sc is a relatively protease-resistant, beta sheet-rich form of the globular membrane protein PrP-c. The temporal distribution of PrP-Sc is of interest when developing early preclinical diagnostic tests, and when examining possible routes of transmission. In this publication, the tissue and cellular distribution of PrP-Sc was examined by immunohistochemistry analysis of formalin fixed tissues from two entire flocks of sheep exposed to the scrapie agent. Accumulations of PrP-Sc were noted in the brain in advanced cases (accompanied by neuronal degeneration). In early cases, PrP-Sc was detected in lymphoid tissue of the alimentary and non-alimentary tract and in the placenta. PrP-Sc colocalized with a marker for follicular dendritic cells in the lymphoid system and in fetal trophoblast cells of the placentomes, although not in the apposing maternal uterine tissues. These findings are consistent with earlier reports and support a transmission model based on shedding of the infectious agent in placental tissue, uptake through the gut and transport to the central nervous system through the peripheral nerves, particularly in the gastrointestinal tract. Precise location of the earliest PrP-Sc accumulations will be useful in designing diagnostic tests for young animals.