Follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions
Follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions
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DOI：
10.1016/s0006-291x(02)00476-x
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发表时间：
2002-06-07
影响因子：
3.1
通讯作者：
Shin, RW
中科院分区：
文献类型：
--
作者：
Kitamoto, T;Mohri, S;Shin, RW
传染性朊病毒病在淋巴器官内引发感染，在外周感染的早期阶段朊病毒感染性在淋巴器官内积累。在小鼠适应性朊病毒感染中，朊病毒蛋白（PrP）的异常亚型（PrPSc）在淋巴器官内的滤泡树突状细胞中积累。然而，人朊病毒并没有引起PrPSc在野生型小鼠中的积累。在这里，我们报告说，敲入小鼠表达人源化嵌合PrP证明PrPSc，在滤泡树突状细胞积累后，人类朊病毒感染，包括变异克雅氏病。积累的PrPSc由重组PrP组成，但不包括接种的人PrP。在接种后30天检查的所有小鼠的脾脏中均可检测到这些蓄积。脾脏的蠕动也很明显。人源化PrP在脾脏中的转化提供了一种快速和灵敏的生物测定方法，以揭示人朊病毒的感染性。这种模式应有助于预防传染性朊病毒疾病。(C)2002年爱思唯尔科学（美国）。All rights reserved.
Infectious prion diseases initiate infection within lymphoid organs where prion infectivity accumulates during the early stages of peripheral infection. In a mouse-adapted prion infection, an abnormal isoform (PrPSc) of prion protein (PrP) accumulates in follicular dendritic cells within lymphoid organs. Human prions, however, did not cause an accumulation of PrPSc in the wild type mice. Here, we report that knock-in mouse expressing humanized chimeric PrP demonstrated PrPSc, accumulations in follicular dendritic cells following human prion infections, including variant Creutzfeldt-Jakob disease. The accumulated PrPSc consisted of recombinant PrP, but not of the inoculated human PrP. These accumulations were detectable in the spleens of all mice examined 30 days post-inoculation. Infectivity of the spleen was also evident. Conversion of humanized PrP in the spleen provides a rapid and sensitive bioassay method to uncover the infectivity of human prions. This model should facilitate the prevention of infectious prion diseases. (C) 2002 Elsevier Science (USA). All rights reserved.