Humanized knock-in mice expressing chimeric prion protein showed varied susceptibility to different human prions
Humanized knock-in mice expressing chimeric prion protein showed varied susceptibility to different human prions
复制标题
DOI：
10.1016/s0002-9440(10)63613-9
复制
发表时间：
2003-12-01
影响因子：
6
通讯作者：
Kitamoto, T
中科院分区：
文献类型：
--
作者：
Taguchi, Y;Mohri, S;Kitamoto, T
小鼠在短的潜伏期内就能有效地传播人朊病毒，这不仅是研究人朊病毒的重要工具，而且是可靠的诊断工具。我们最近产生了一个罚款的敲入小鼠表达一个独特的人-鼠嵌合PrP（Ki-ChM小鼠），它具有小鼠特异性的残基，几乎只有在C-末端部分翻译后修饰，在这里，我们试图传输各种人朊病毒，以评估小鼠的易感性。不同感染朊病毒的易感性差异很大：对MM 1型和MV 1型散发性克雅氏病（CJD）高度易感，发病时间约为150天，对M232 R突变的家族性CJD和无淀粉样斑块的硬脑膜移植相关性CJD（dCJD）高度易感;对MM 2型散发性CJD和变异型CJD较不敏感，有些小鼠没有任何传播迹象;对VV 2型散发性CJD和伴有淀粉样斑块的dCJD完全耐药。Ki-ChM小鼠实现的相当短的潜伏期表明有新的方法来产生在非常短的潜伏期内患上朊病毒疾病的小鼠。我们比较了Ki-ChM与其他先前转基因小鼠的特征易感性，并讨论了开发对人朊病毒易感的基因工程小鼠的前景。
Mice to which human prions efficiently transmit in short incubation periods are valuable not only as research tools of human prions but also as reliable diagnostic tools. We recently produced a fine of knock-in mouse expressing a unique human-mouse chimeric PrP (Ki-ChM mouse), which has mouse-specific residues practically only at the C-terminal part after posttranslational modification, and here we attempted transmission of various human prions to assess the susceptibility profile of the mouse. Susceptibility varied considerably depending on prions inoculated: highly susceptible to MM1 and MV1 types of sporadic Creutzfeldt-Jakob disease (CJD), developing disease within similar to150 days, familial CJD with M232R mutation, and dura graft-associated CJD (dCJD) without amyloid plaque; less susceptible to MM2-type sporadic CJD and variant CJD, with some mice lacking any sign of transmission; and totally resistant to VV2 type sporadic CJD and dCJD with amyloid plaque. The rather short incubation time achieved by Ki-ChM mice suggests new approaches to produce mice that develop prion disease with very short incubation periods. We compared the characteristic susceptibility profile of Ki-ChM with those of other precedent transgenic mice and discussed, including the prospects in developing genetically engineered mice susceptible to human prions.