Dramatic reduction of PrP C level and glycosylation in peripheral nerves following PrP knock-out from Schwann cells does not prevent transmissible spongiform encephalopathy neuroinvasion

• Published in: The Journal of neuroscience 2009-12, Vol.29 (49), p.15445-15454
• Main Authors: Bradford, Barry M, Tuzi, Nadia L, Feltri, M Laura, McCorquodale, Caroline, Cancellotti, Enrico, Manson, Jean C
• Format: Article
• Language: English
• Subjects: Animals; Brain - pathology; Brain - physiopathology; Glycosylation; Infectious Disease Incubation Period; Kaplan-Meier Estimate; Mice; Mice, Knockout; Mice, Transgenic; Peripheral Nerves - pathology; Peripheral Nerves - physiopathology; Prion Diseases - pathology; Prion Diseases - physiopathology; Prion Diseases - transmission; PrPC Proteins - genetics; PrPC Proteins - metabolism; PrPSc Proteins - metabolism; Schwann Cells - pathology; Schwann Cells - physiology; Sciatic Nerve - pathology; Sciatic Nerve - physiopathology; Scrapie - pathology; Scrapie - physiopathology; Scrapie - transmission; Time Factors; Vacuoles - pathology; Vacuoles - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.4195-09.2009

Expression of the prion protein (PrP(C)) 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, PrP(C) expression was selectively removed from Schwann cells in vivo. This dramatically reduced total PrP(C) within peripheral nerves by 90%, resulting in the selective loss of glycosylated PrP(C) 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.