Brandner S, Isenmann S, Raeber A, Fischer M, Sailer A, Kobayashi Y, Marino S, Weissmann C, Aguzzi A
Department of Pathology, University Hospital, Zürich, Switzerland.
Nature. 1996 Jan 25;379(6563):339-43. doi: 10.1038/379339a0.
Accumulation of the prion protein PrPSc, a pathological and protease-resistant isoform of the normal host protein PrPC, is a feature of prion disease such as scrapie. It is still unknown whether scrapie pathology comes about by neurotoxicity of PrPSc, acute depletion of PrPC, or some other mechanism. Here we investigate this question by grafting neural tissue overexpressing PrPC into the brain of PrP-deficient mice which are scrapie-resistant and do not propagate infectivity. After intracerebral inoculation with scrapie prions, the grafts accumulated high levels of PrPSc and infectivity and developed the severe histopathological changes characteristic of scrapie. Moreover, substantial amounts of graft-derived PrPSc migrated into the host brain. Even 16 months after inoculation no pathological changes were seen in PrP-deficient tissue, not even in the immediate vicinity of the grafts. Therefore, in addition to being resistant to scrapie infection, brain tissue devoid of PrPC is not damaged by exogenous PrPSc.
朊病毒蛋白PrPSc是正常宿主蛋白PrPC的一种病理性且抗蛋白酶的异构体，其蓄积是诸如羊瘙痒症等朊病毒疾病的一个特征。目前仍不清楚羊瘙痒症的病理变化是由PrPSc的神经毒性、PrPC的急性耗竭还是其他某种机制引起的。在此，我们通过将过表达PrPC的神经组织移植到抗羊瘙痒症且不传播感染性的PrP缺陷小鼠脑内来研究这个问题。在用羊瘙痒症朊病毒进行脑内接种后，移植组织蓄积了高水平的PrPSc和感染性，并出现了羊瘙痒症特有的严重组织病理学变化。此外，大量源自移植组织的PrPSc迁移到宿主脑内。即使在接种16个月后，PrP缺陷组织中也未观察到病理变化，甚至在移植组织紧邻区域也未观察到。因此，除了对羊瘙痒症感染具有抗性外，缺乏PrPC的脑组织不会受到外源性PrPSc的损害。
