Cytoplasmic expression of mouse prion protein causes severe toxicity in Caenorhabditis elegans.
Cytoplasmic expression of mouse prion protein causes severe toxicity in Caenorhabditis elegans.
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DOI：
10.1016/j.bbrc.2008.05.132
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发表时间：
2008-08
影响因子：
3.1
通讯作者：
Kyung-Won Park;Liming Li
中科院分区：
文献类型：
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作者：
Kyung-Won Park;Liming Li
为了验证秀丽线虫是否可以作为研究普恩病毒的模式生物，我们建立了表达小鼠普恩蛋白胞浆形式MoPrP(23-231)的转基因线虫，该蛋白缺乏N-末端信号序列和C-末端糖基磷脂酰肌醇(GPI)锚点。我们在这里报道了表达MoPrP(23-231)-CFP的转基因虫子表现出广泛的不同的表型：从正常的生长和发育，减少的运动和发育延迟，完全瘫痪和发育停止，到胚胎死亡。在表现这些不同表型的动物中也产生了类似水平的MoPrP(23-231)-CFP，表明MoPrP(23-231)-CFP可能错误折叠成了不同的有毒物种。结合PrP突变影响PrP致病机制也影响线虫毒力表型的观察，我们得出结论，PrP蛋白折叠机制在哺乳动物和线虫中是相似的。因此，秀丽线虫可以成为一种有用的蛋白质研究的模式生物。
To test if Caenorhabditis elegans could be established as a model organism for prion study, we created transgenic C. elegans expressing the cytosolic form of the mouse prion protein, MoPrP(23-231), which lacks the N-terminal signal sequence and the C-terminal glycosylphosphatidylinisotol (GPI) anchor site. We report here that transgenic worms expressing MoPrP(23-231)-CFP exhibited a wide range of distinct phenotypes: from normal growth and development, reduced mobility and development delay, complete paralysis and development arrest, to embryonic lethality. Similar levels of MoPrP(23-231)-CFP were produced in animals exhibiting these distinct phenotypes, suggesting that MoPrP(23-231)-CFP might have misfolded into distinct toxic species. In combining with the observation that mutations in PrP that affect prion pathogenesis also affect the toxic phenotypes in C. elegans, we conclude that the prion protein-folding mechanism is similar in mammals and C. elegans. Thus, C. elegans can be a useful model organism for prion research.