Telling G C, Scott M, Mastrianni J, Gabizon R, Torchia M, Cohen F E, DeArmond S J, Prusiner S B
Department of Neurology, University of California, San Francisco 94143, USA.
Cell. 1995 Oct 6;83(1):79-90. doi: 10.1016/0092-8674(95)90236-8.
Transgenic (Tg) mice expressing human (Hu) and chimeric prion protein (PrP) genes were inoculated with brain extracts from humans with inherited or sporadic prion disease to investigate the mechanism by which PrPC is transformed into PrPSc. Although Tg(HuPrP) mice expressed high levels of HuPrPC, they were resistant to human prions. They became susceptible to human prions upon ablation of the mouse (Mo) PrP gene. In contrast, mice expressing low levels of the chimeric transgene were susceptible to human prions and registered only a modest decrease in incubation times upon MoPrP gene disruption. These and other findings argue that a species-specific macromolecule, provisionally designated protein X, participates in prion formation. While the results demonstrate that PrPSc binds to PrPC in a region delimited by codons 96 to 167, they also suggest that PrPC binds protein X through residues near the C-terminus. Protein X might function as a molecular chaperone in the formation of PrPSc.
将表达人（Hu）和嵌合朊病毒蛋白（PrP）基因的转基因（Tg）小鼠接种来自患有遗传性或散发性朊病毒病的人类的脑提取物，以研究PrPC转化为PrPSc的机制。尽管Tg（HuPrP）小鼠表达高水平的HuPrPC，但它们对人朊病毒具有抗性。在敲除小鼠（Mo）PrP基因后，它们对人朊病毒变得易感。相比之下，表达低水平嵌合转基因的小鼠对人朊病毒易感，并且在MoPrP基因破坏后仅在潜伏期有适度缩短。这些以及其他发现表明，一种物种特异性大分子，暂定为蛋白X，参与朊病毒形成。虽然结果表明PrPSc在由密码子96至167界定的区域内与PrPC结合，但它们还表明PrPC通过C末端附近的残基与蛋白X结合。蛋白X可能在PrPSc形成中起分子伴侣的作用。
