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

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 ro...

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Bibliographic Details
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
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.4195-09.2009