Brandner S, Raeber A, Sailer A, Blättler T, Fischer M, Weissmann C, Aguzzi A
Institute of Neuropathology, University Hospital, Zürich, Switzerland.
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13148-51. doi: 10.1073/pnas.93.23.13148.
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.
缺乏PrPC（Prnp%）的小鼠对羊瘙痒病具有抗性，且不允许感染因子（朊病毒）繁殖。移植到Prnp%小鼠大脑中的表达PrPC的神经外胚层组织（而非周围组织）始终会出现羊瘙痒病特异性病理变化，并在接种后允许朊病毒复制。将羊瘙痒病朊病毒经眼内接种到野生型小鼠体内后，其可在16周内有效扩散至中枢神经系统。为确定PrPC对于羊瘙痒病传播是否必要，我们将朊病毒经眼内接种到含有过表达PrP的神经移植物的Prnp%小鼠体内。在长达66周的时间里，移植物中均未检测到脑病或蛋白酶抗性PrP（PrPSc）。由于移植的表达PrP的细胞引发了可能干扰朊病毒传播的免疫反应，我们培育了对PrP具有免疫耐受性的Prnp%小鼠，并将产生PrP的神经外胚层组织移植到它们体内。同样，经眼内接种并未导致产生PrP的移植物发病。这些结果表明，PrP对于朊病毒沿神经通路传播是必要的。
