Three hamster species with different scrapie incubation times and neuropathological features encode distinct prion proteins.
Three hamster species with different scrapie incubation times and neuropathological features encode distinct prion proteins.
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具有不同痒病孵化时间和神经病理学特征的三种仓鼠物种编码不同的朊病毒蛋白。
DOI：
10.1128/mcb.10.3.1153-1163.1990
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发表时间：
1990
影响因子：
5.3
通讯作者：
Prusiner,SB
中科院分区：
文献类型：
--
作者：
Lowenstein,DH;Butler,DA;Westaway,D;McKinley,MP;DeArmond,SJ;Prusiner,SB
鉴于朊病毒蛋白（PrP）在实验性瘙痒症的传播和发病机制中的关键作用，我们研究了PrP基因及其蛋白产物在三种仓鼠中的作用，中国仓鼠（CHa），亚美尼亚仓鼠（AHa）和叙利亚仓鼠（SHa），每种仓鼠都有独特的瘙痒症潜伏期。传代研究表明，宿主物种，而不是来源的瘙痒症朊病毒，确定每个物种的孵育时间，和组织化学研究的仓鼠与瘙痒症的临床体征揭示了特征性的神经病理学模式。北方（RNA）分析显示来自CHa、AHa和SHa仓鼠的PrP mRNA的大小分别为2.5、2.4和2.1个碱基。免疫印迹表明，PrP亚型的大小相似（33至35千道尔顿），然而，单克隆抗体13A5提出的SHa PrP不与CHa或AHa PrP分子反应。三个预测的氨基酸序列的比较显示，每个是不同的。此外，独特区分三种仓鼠物种的PrP开放阅读框架内的差异在11个氨基酸的亲水性片段内，其包括与近交系小鼠中的瘙痒病孵育时间和人类的遗传性朊病毒疾病相关的多态性。该区域的单一多态性与给定仓鼠物种或小鼠近交系的淀粉样蛋白斑块的存在或不存在相关。我们的研究结果表明，在三个相关物种的羊瘙痒症的独特的分子，病理和临床特征，并与宿主PrP的分子特性在确定羊瘙痒症的潜伏期和神经病理学特征中起着关键作用的假设是一致的。
Given the critical role of the prion protein (PrP) in the transmission and pathogenesis of experimental scrapie, we investigated the PrP gene and its protein products in three hamster species, Chinese (CHa), Armenian (AHa), and Syrian (SHa), each of which were found to have distinctive scrapie incubation times. Passaging studies demonstrated that the host species, and not the source of scrapie prions, determined the incubation time for each species, and histochemical studies of hamsters with clinical signs of scrapie revealed characteristic patterns of neuropathology. Northern (RNA) analysis showed the size of PrP mRNA from CHa, AHa, and SHa hamsters to be 2.5, 2.4, and 2.1 kilobases, respectively. Immunoblotting demonstrated that the PrP isoforms were of similar size (33 to 35 kilodaltons); however, the monoclonal antibody 13A5 raised against SHa PrP did not react with the CHa or AHa PrP molecules. Comparison of the three predicted amino acid sequences revealed that each is distinct. Furthermore, differences within the PrP open reading frame that uniquely distinguish the three hamster species are within a hydrophilic segment of 11 amino acids that includes polymorphisms linked to scrapie incubation times in inbred mice and an inherited prion disease of humans. Single polymorphisms in this region correlate with the presence or absence of amyloid plaques for a given hamster species or mouse inbred strain. Our findings demonstrate distinctive molecular, pathological, and clinical characteristics of scrapie in three related species and are consistent with the hypothesis that molecular properties of the host PrP play a pivotal role in determining the incubation time and neuropathological features of scrapie.