Normal host prion protein (PrPc) is required for scrapie spread within the central nervous system
Normal host prion protein (PrPc) is required for scrapie spread within the central nervous system
复制标题
DOI：
10.1073/pnas.93.23.13148
复制
发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Aguzzi, A
中科院分区：
文献类型：
--
作者：
Brandner, S;Raeber, A;Aguzzi, A
缺乏PrPC （Prnp(o/o)）的小鼠对痒病具有抗性，并且不允许感染因子（朊病毒）的传播。将表达prpc的神经外胚层组织移植到Prnp（o/o）大脑中，而不是周围组织，一致表现出瘙痒病特异性病理，并在接种后允许朊病毒复制。将痒病朊病毒眼内注入野生型小鼠，在16周内有效地扩散到中枢神经系统。为了确定痒病传播是否需要PrPC，我们将朊病毒接种到含有过表达prp的神经移植物的Prnp（o/o）小鼠眼内。在长达66周的移植物中，既没有检测到脑病，也没有检测到蛋白酶抗性PrP (PrPSc)，因为移植的表达PrP的细胞引发了可能干扰朊病毒传播的免疫反应，我们产生了对PrP免疫耐受的Prnp（o/o）小鼠，并将其植入产生PrP的神经外胚层组织。再次，眼内接种不会导致产生PrP的移植物疾病。这些结果表明PrP是朊病毒沿神经通路传播所必需的。
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.