NR AXJS
AU Bradford,B.; Manson,J.; Brophy,P.; Tuzi,N.
TI PrP Expression in Schwann Cells is not Required for Transmissible Spongiform Encephalopathy Neuroinvasion
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.149
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Transmissible spongiform encephalopathies (TSEs) such as scrapie are neurodegenerative diseases characterised by long incubation periods and spongiform vacuolar pathology in the central nervous system (CNS). The expression of prion protein (PrP) is a requirement for the establishment and development of TSE disease. The process of agent replication in the periphery and invading the CNS is termed neuroinvasion. The exact mechanism of transport of the infectious agent is still unknown, and the roles of various cell types involved in this process are still to be determined. The TSE neuroinvasive process is postulated to be dependent upon a continuous chain of PrP expressing tissue between the infection site and the CNS, with the most likely candidate being the peripheral nervous system (PNS). However, measured transport rates of infection do not match rates of fast or slow axonal transport suggesting some other mechanism of transport. Myelinating Schwann cells of the PNS express PrP when associated with PrP expressing nerve axons and are capable of serially propagating the agent in vitro.
Transgenic mice possessing a Schwann cell specific knockout of the PrP gene were produced using the Cre / loxP system to test the hypothesis that Schwann cells are involved in TSE neuroinvasion. Following Cre-mediated recombination in these mice a 90 % reduction in total PrP expression and an altered PrP glycoform pattern were observed in peripheral nervous tissue. These mice were infected with mouse-adapted scrapie agents ME7 and 139A via intracerebral, intraperitoneal and oral routes of infection. No differences in incubation period or central nervous system pathology were observed when compared with peripherally infected control genotype mice. These results suggest that PrP expression in Schwann cells is not required for TSE neuroinvasion.
AD B. Manson,J. Bradford, N. Tuzi, Roslin Institute, Neuropathogenesis Unit, UK; P. Brophy, University of Edinburgh, Centre for Neuroscience, UK
SP englisch
PO Schottland