Normal host prion protein (PrPc) is required for scrapie spread within the central nervous system

Mice 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) 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, me generated Prnp(o/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.