title: Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system.
abstract: Mice devoid of PrPC (Prnp%) are resistant to scrapie and do not allow propagation of the infectious agent (prion). PrPC-expressing neuroectodermal tissue grafted into Prnp% brains but not the surrounding tissue consistently exhibits scrapie-specific pathology and allows prion replication after inoculation. Scrapie prions administered intraocularly into wild-type mice spread efficiently to the central nervous system within 16 weeks. To determine whether PrPC is required for scrapie spread, we inoculated prions intraocularly into Prnp% mice containing a PrP-overexpressing neurograft. Neither encephalopathy nor protease-resistant PrP (PrPSc) were detected in the grafts for up to 66 weeks. Because grafted PrP-expressing cells elicited an immune response that might have interfered with prion spread, we generated Prnp% mice immunotolerant to PrP and engrafted them with PrP-producing neuroectodermal tissue. Again, intraocular inoculation did not lead to disease in the PrP-producing graft. These results demonstrate that PrP is necessary for prion spread along neural pathways.
authors.affiliation: Institute of Neuropathology, University Hospital, Zürich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Brandner
authors.forename: A
authors.initials: A
authors.lastname: Raeber
authors.forename: A
authors.initials: A
authors.lastname: Sailer
authors.forename: T
authors.initials: T
authors.lastname: Blättler
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: C
authors.initials: C
authors.lastname: Weissmann
authors.forename: A
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000818:Animals; D016380:Brain Tissue Transplantation / Q000473:pathology / Q000502:physiology*; D002421:Caudate Nucleus / Q000473:pathology* / Q000821:virology; D002454:Cell Differentiation; D004475:Ectoderm / Q000637:transplantation; D016332:Fetal Tissue Transplantation / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000166:cytology / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000473:pathology; D011328:Prions / Q000096:biosynthesis* / Q000235:genetics*; D011699:Putamen / Q000473:pathology* / Q000821:virology; D012608:Scrapie / Q000473:pathology / Q000635:transmission*
chemical_list: D011328:Prions