Studies on polymorphism of the prion protein gene in familial Creutzfeldt-Jakob disease.

家族性克雅氏病朊病毒蛋白基因多态性研究。

基本信息

批准号：
02454245
负责人：
TATEISHI Jun
金额：
$ 4.48万
依托单位：
Kyusyu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454245/
关键词：
Creutzfeld-Jakob disease Gerstmann-Straussler syndrome prion protein polymorphism 多型性

项目摘要

We examined polymorphism of prion protein open reading frame. We found out several point mutations and insertional polymorphism. At first, we reported that codon 102 or codon 117 point mutation was linked to Gerstmann-Straussler syndrome. We also found codon 129 mutation, codon 200 mutation and 168 bp insertion in the proline-glycine rich repetitive portion of prion protein. To examine the precise localization of prion protein, we established a new pretreatment. designated as hydrolytic autoclaving. This pretreatment could reveal abnormal prion protein accumulations in the gray matter of the central nervous system. This diffuse gray matter stainings were documented in all patients with Creutzfeldt-Jakob disease. Prion protein immunostainings were similar to synaptophysin immunostainings. To examine precisely, we performed double immunolabelling using anti-prion protein and anti-synaptophysin. Both immunoreactions were colocalized in the same synaptic structures. Therefore, we reported … More that the major localization of abnormal prion protein is the synaptic structures in patients with sporadic Creutzfeldt-Jakob disease.We immunohistochemically examined tissue sections from patients with prion protein polymorphism using hydrolytic autoclaving enhancement. Abnormal prion protein accumulations could be classified into plaque formations(plaque-type)and the diffuse gray matter stainings including synaptic structures(synaptic-type). Both insertional polymorphism and a point mutation in codon 102, 117/129, 129 result in plaque-type prion protein accumulations. The patients with codon 102 mutation also have synaptic type prion protein accumulations. However, a point mutation in codon 200 did not show plaque-type accumulations, and only showed synaptic-type prion protein accumulations. Likewise, sporadic Creutzfeldt-Jakob disease patients without any known mutations only have synaptic-type accumulations. These results imply that the primary structures of prion protein influence in the phenotype of prion protein disease, especially in abnormal prion protein distributions of the central nervous system. Less

我们检查了朊病毒蛋白开放阅读框的多态性，我们发现了一些点突变和插入多态性。首先，我们报道了密码子102或密码子117点突变与格斯特曼-斯特劳斯勒综合征有关。我们还发现了密码子129突变、密码子200。朊病毒蛋白富含脯氨酸-甘氨酸的重复部分中的突变和 168 bp 插入为了检查朊病毒蛋白的精确定位，我们建立了一个序列。新的预处理被称为水解高压灭菌，这种预处理可以揭示中枢神经系统灰质中的异常朊病毒蛋白积累，这种弥漫性灰质染色与突触素免疫染色相似。为了精确检查，我们使用抗朊病毒蛋白和抗突触素进行双重免疫标记，两种免疫反应共定位于同一区域。因此，我们报道异常朊病毒蛋白的主要定位是散发性克雅氏病患者的突触结构。我们使用水解高压灭菌增强法对朊病毒蛋白多态性患者的组织切片进行了免疫组织化学检查。可分为斑块形成（斑块型）和包括突触结构的弥漫性灰质染色（突触型）。密码子 102、117/129、129 的多态性和点突变导致斑块型朊病毒蛋白积聚。密码子 102 突变的患者也有突触型朊病毒蛋白积聚，而密码子 200 的点突变则没有表现出斑块型朊病毒蛋白积聚。类似地，没有任何已知突变的散发性克雅氏病患者仅具有突触型朊病毒蛋白积累。这些结果表明，朊病毒蛋白的主要结构对朊病毒蛋白疾病的表型影响较小，尤其是在中枢神经系统的异常朊病毒蛋白分布中。