Identification of the pathological prion protein allotypes in scrapie-infected heterozygous bank voles (Clethrionomys glareolus) by high-performance liquid chromatography-mass spectrometry
Identification of the pathological prion protein allotypes in scrapie-infected heterozygous bank voles (Clethrionomys glareolus) by high-performance liquid chromatography-mass spectrometry
复制标题
DOI：
10.1016/j.chroma.2005.04.035
复制
发表时间：
2005-07-15
影响因子：
4.1
通讯作者：
Agrimi, U
中科院分区：
文献类型：
--
作者：
Cartoni, C;Schininà, ME;Agrimi, U
朊病毒蛋白（PrP）病理亚型的脑形成是朊病毒疾病的关键分子事件。河岸田鼠（Clethrionomys glareolus）是一种对自然痒病高度敏感的啮齿动物。河岸田鼠PrP基因在密码子109处存在多态性（Met/IIe）。在这里，我们表明，纯合子109（Met/Met）田鼠的孵化时间短于杂合子109（Met/IIe）田鼠实验挑战后，与三种不同的羊瘙痒病分离株。HPLC-MS/MS方法进行了优化，并应用于研究是否在杂合子动物PrP同种异型能够进行病理转换。结果表明，朊病毒蛋白的两种同种异型都参与了病理沉积。(c)2005 Elsevier B. V.保留所有权利。
Cerebral formation of the pathological isoform of the prion protein (PrP) is a crucial molecular event in prion diseases. The bank vole (Clethrionomys glareolus) is a rodent species highly susceptible to natural scrapie. The PrP gene of bank vole is polymorphic (Met/IIe) at codon 109. Here we show that homozygous 109(Met/Met) voles have incubation times shorter than heterozygous 109(Met/IIe) voles after experimental challenge with three different scrapie isolates. An HPLC-MS/MS method was optimized and applied to investigate whether in heterozygous animals both PrP allotypes are able to undergo pathological conversion. The results demonstrate that both allotypes of the prion protein participate to pathological deposition. (c) 2005 Elsevier B.V. All rights reserved.