Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein.
Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein.
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DOI：
10.1186/2051-5960-1-74
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发表时间：
2013-11-13
影响因子：
7.1
通讯作者：
Kitamoto T
中科院分区：
文献类型：
--
作者：
Kobayashi A;Iwasaki Y;Otsuka H;Yamada M;Yoshida M;Matsuura Y;Mohri S;Kitamoto T
散发性Creutzfeldt-Jakob病根据朊病毒蛋白（PrP）基因多态性密码子129（M或V）的基因型和脑中异常同种型PrP（PrPSc）的类型（1或2）进行分类。目前分类系统中最复杂的实体是MV 2，因为它显示出广泛的表型变异，即，MV 2皮质型（MV 2C）、MV 2伴库鲁斑（MV 2K）或混合型（MV 2K + C）。为了解决其复杂的发病机制，我们进行了全面的分析，MV 2的三个亚组的基础上，组织病理学，分子和传播特性。在组织病理学和分子生物学分析中，MV 2C显示出与MM 2皮质型（MM 2C）的密切相似性，并且可以容易地与其他MV 2亚组区分开。MV 2K和MV 2K + C的分子类型和传递类型相同，两者的唯一区别是存在MV 2C/MM 2C的皮质病理学特征。MV 2K或MV 2K + C的显著分子特征是2型PrPSc和中间型PrPSc的混合物，其显示介于1型和2型PrPSc之间的中间电泳迁移率。使用PrP人源化小鼠的建模实验表明，MV 2K含有中间型PrPSc与129 M基因型的混合物（Mi PrPSc）和2型PrPSc（129 V基因型）（V2 PrPSc）源自V2 PrPSc，而MV 2C + K也可能含有129 M基因型和皮质病理学的2型PrPSc在另一个实施方案中，使用除了M1和V2 PrPSc之外对PrP人源化小鼠缺乏感染性的M2 C PrPSc。综上所述，本研究表明MV 2的表型异质性源于其不同的PrPSc来源。
Sporadic Creutzfeldt-Jakob disease is classified according to the genotype at polymorphic codon 129 (M or V) of the prion protein (PrP) gene and the type (1 or 2) of abnormal isoform of PrP (PrPSc) in the brain. The most complicated entity in the current classification system is MV2, since it shows wide phenotypic variations, i.e., MV2 cortical form (MV2C), MV2 with kuru plaques (MV2K), or a mixed form (MV2K + C). To resolve their complicated pathogenesis, we performed a comprehensive analysis of the three MV2 subgroups based on histopathological, molecular, and transmission properties. In histopathological and molecular analyses, MV2C showed close similarity to MM2 cortical form (MM2C) and could be easily discriminated from the other MV2 subgroups. By contrast, MV2K and MV2K + C showed the same molecular type and the same transmission type, and the sole difference between MV2K and MV2K + C was the presence of cortical pathology characteristic of MV2C/MM2C. The remarkable molecular feature of MV2K or MV2K + C was a mixture of type 2 PrPSc and intermediate type PrPSc, which shows intermediate electrophoretic mobility between types 1 and 2 PrPSc. Modeling experiments using PrP-humanized mice indicated that MV2K contains a mixture of intermediate type PrPSc with the 129M genotype (Mi PrPSc) and type 2 PrPSc with the 129V genotype (V2 PrPSc) that originated from V2 PrPSc, whereas MV2C + K may also contain type 2 PrPSc with the 129M genotype and cortical pathology (M2C PrPSc) that lacks infectivity to the PrP-humanized mice in addition to Mi and V2 PrPSc. Taken together, the present study suggests that the phenotypic heterogeneity of MV2 stems from their different PrPSc origin(s).
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DOI：
10.1016/s0006-291x(02)00476-x
发表时间：
2002-06-07
影响因子：
3.1
作者：
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影响因子：
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影响因子：
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通讯作者：
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DOI：
10.1016/j.bbrc.2008.03.014
发表时间：
2008-05-16
影响因子：
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作者：
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