NeuroCentre, National and OIE Reference Laboratories for BSE and Scrapie, Division of Experimental Clinical Research, Vetsuisse Faculty, University of Berne, Berne, Switzerland.
PLoS One. 2011;6(11):e27510. doi: 10.1371/journal.pone.0027510. Epub 2011 Nov 11.
The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrP(d)). To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical scrapie to transgenic mice over-expressing the ovine prion protein (tg338). The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical scrapie isolates and the Nor98, an atypical scrapie isolate from Norway. Together with published data, our results suggest that atypical scrapie is caused by a uniform type of prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent proteinase K-resistant prion protein fragment in atypical scrapie consists of two separate, unglycosylated peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research.
绵羊和山羊感染的非典型羊瘙痒病的发病机制仍不清楚。在之前的研究中，我们证明了瑞士影响小反刍动物的非典型羊瘙痒病在病理朊病毒蛋白（PrP(d)）的神经解剖分布上存在差异。为了研究这些差异是否取决于宿主相关因素还是病原体相关因素，我们将非典型羊瘙痒病传染给过度表达绵羊朊病毒蛋白（tg338）的转基因小鼠。携带瑞士非典型羊瘙痒病分离株和挪威非典型羊瘙痒病分离株 Nor98 的 tg338 小鼠的临床、神经病理学和分子表型相似。结合已发表的数据，我们的研究结果表明，非典型羊瘙痒病是由一种统一类型的朊病毒引起的，而小反刍动物中观察到的表型差异可能与宿主有关。引人注目的是，通过使用改良的 SDS-PAGE 技术，我们确定了非典型羊瘙痒病中显著的蛋白水解酶抗性朊病毒蛋白片段由两个单独的、未糖基化的肽组成，分子量约为 5 和 8 kDa。这些发现与动物和人类中其他朊病毒疾病的发现相似，并为未来的比较研究奠定了基础。
