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prion蛋白开放阅读框的多态性。我们发现了几个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Gerstmann-Straussler综合征有关。我们还发现密码子129突变，密码子200突变和168 bp插入pr甘氨酸富含prion蛋白的重复性部分。为了检查prion蛋白的精确定位，我们建立了一种新的预处理。设计为水解高压灭菌。这种预处理可能揭示中枢神经系统灰质中的异常prion蛋白积累。在所有Creutzfeldt-Jakob病患者中都记录了这种弥漫性灰质染色。 prion蛋白免疫抑制类似于突触素免疫抑制剂。为了准确检查，我们使用抗蛋白质蛋白和抗突触蛋白进行了双重免疫标记。两种免疫反应均在相同的合成结构中共定位。因此，我们报告的……更多的是，异常的prion蛋白的主要定位是散发性creutzfeldt-jakob病的患者的合成结构。我们使用水解自动脱脂剂增强了免疫组织化学检查了来自Prion蛋白多态性的患者的免疫组织化学检查。异常的prion蛋白积累可以分为斑块地层（斑块类型）和包括突触结构（突触类型）的弥漫性灰质染色。密码子102、117/129、129中的插入多态性和点突变都导致斑块型prion蛋白积累。密码子102突变的患者还具有合成型prion蛋白的积累。但是，密码子200中的点突变并未显示斑块型积累，并且仅显示合成型prion蛋白的积累。同样，没有任何已知突变的零星creutzfeldt-jakob病患者只有突触型积累。这些结果表明，prion蛋白在prion蛋白疾病的表型中的主要结构，尤其是在中枢神经系统的异常prion蛋白分布中。较少的