Aguzzi A, Klein M A, Musahl C, Raeber A J, Blättler T, Hegyi I, Frigg R, Brandner S
Department of Pathology, University of Zürich, Switzerland.
Essays Biochem. 1998;33:133-47. doi: 10.1042/bse0330133.
For the study of prion neurotoxicity, we used neural-grafting techniques: mice devoid of the normal host prion protein (Prnp% mice) received a neural graft and were intracerebrally infected with mouse prions. The growth and differentiation properties of neural grafts were defined. Growth of embryonic neuroectodermal tissue was optimal at gestational days 12.5-13.5. The blood-brain barrier is reconstituted after 7 weeks in most animals. Scrapie-infected PrPC-expressing grafts develop a severe spongiform encephalopathy and contain proteinase-resistant protein and infectivity. Infected grafts deliver high amounts of prions to the host brain without eliciting disease. Infected grafts show a progressive disruption of the blood-brain barrier. Following intraocular prion inoculation of a transplanted Prnp% mouse, prions do not reach the intracerebral graft, indicating that PrP expression is required for propagation along the optic tract.
为了研究朊病毒神经毒性，我们采用了神经移植技术：缺乏正常宿主朊病毒蛋白的小鼠（Prnp%小鼠）接受神经移植，并经脑内接种小鼠朊病毒。确定了神经移植的生长和分化特性。胚胎神经外胚层组织在妊娠第12.5 - 13.5天生长最佳。大多数动物在7周后血脑屏障得以重建。感染羊瘙痒病的表达PrPC的移植物会发展为严重的海绵状脑病，并含有蛋白酶抗性蛋白和传染性。受感染的移植物会向宿主脑内输送大量朊病毒，但不会引发疾病。受感染的移植物显示出血脑屏障的渐进性破坏。对移植的Prnp%小鼠进行眼内接种朊病毒后，朊病毒无法到达脑内移植物，这表明沿视神经束传播需要PrP表达。
