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 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.
Bradford
Barry M
BM
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9PS, United Kingdom.
Tuzi
Nadia L
NL
Feltri
M Laura
ML
McCorquodale
Caroline
C
Cancellotti
Enrico
E
Manson
Jean C
JC
D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D006031:Glycosylation; D055256:Infectious Disease Incubation Period; D053208:Kaplan-Meier Estimate; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism; D017096:Prion Diseases / Q000473:pathology / Q000503:physiopathology* / Q000635:transmission*; D012583:Schwann Cells / Q000473:pathology / Q000502:physiology*; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D012608:Scrapie / Q000473:pathology / Q000503:physiopathology / Q000635:transmission; D013997:Time Factors; D014617:Vacuoles / Q000473:pathology / Q000502:physiology
D018621:PrPC Proteins; D018620:PrPSc Proteins