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

1996; National Academy of Sciences; Volume: 93; Issue: 23 Linguagem: Inglês

10.1073/pnas.93.23.13148

1091-6490

Sebastian Brandner, Alex J. Raeber, Andreas W. Sailer, Thomas Blättler, Marek Fischer, Charles Weissmann, Adriano Aguzzi,

Neurological diseases and metabolism

Mice devoid of PrP C ( Prnp o/o ) are resistant to scrapie and do not allow propagation of the infectious agent (prion). PrP C -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 PrP C 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 (PrP Sc ) 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 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.