Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system
S Brandner, A Raeber, A Sailer… - Proceedings of the …, 1996 - National Acad Sciences
S Brandner, A Raeber, A Sailer, T Blättler, M Fischer, C Weissmann, A Aguzzi
Proceedings of the National Academy of Sciences, 1996•National Acad SciencesMice devoid of PrPC (Prnp o/o) are resistant to scrapie and do not allow propagation of the
infectious agent (prion). PrPC-expressing neuroectodermal tissue grafted into Prnp o/o
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 o/o …
infectious agent (prion). PrPC-expressing neuroectodermal tissue grafted into Prnp o/o
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 o/o …
Mice devoid of PrPC (Prnpo/o) are resistant to scrapie and do not allow propagation of the infectious agent (prion). PrPC-expressing neuroectodermal tissue grafted into Prnpo/o 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 Prnpo/o 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 Prnpo/o 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.
National Acad Sciences