RT Journal Article SR Electronic T1 Dramatic Reduction of PrPC Level and Glycosylation in Peripheral Nerves following PrP Knock-Out from Schwann Cells Does Not Prevent Transmissible Spongiform Encephalopathy Neuroinvasion JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 15445 OP 15454 DO 10.1523/JNEUROSCI.4195-09.2009 VO 29 IS 49 A1 Barry M. Bradford A1 Nadia L. Tuzi A1 M. Laura Feltri A1 Caroline McCorquodale A1 Enrico Cancellotti A1 Jean C. Manson YR 2009 UL http://www.jneurosci.org/content/29/49/15445.abstract AB Expression of the prion protein (PrPC) is a requirement for host susceptibility to the transmissible spongiform encephalopathies (TSEs) and thought to be necessary for the replication and transport of the infectious agent. The mechanism of TSE neuroinvasion is not fully understood, although the routing of infection has been mapped through the peripheral nervous system (PNS) and Schwann cells have been implicated as a potential conduit for transport of the TSE infectious agent. To address whether Schwann cells are a requirement for spread of the TSE agent from the site of infection to the CNS, PrPC expression was selectively removed from Schwann cells in vivo. This dramatically reduced total PrPC within peripheral nerves by 90%, resulting in the selective loss of glycosylated PrPC species. Despite this, 139A and ME7 mouse-passaged scrapie agent strains were efficiently replicated and transported to the CNS following oral and intraperitoneal exposure. Thus, the myelinating glial cells within the PNS do not appear to play a significant role in TSE neuroinvasion.