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

我们检测了朊病毒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。我们首先报道了102或117密码子点突变与Gerstmann-Straussler综合征有关。在朊病毒蛋白富含脯氨酸-甘氨酸的重复序列中，我们还发现了密码子129突变、密码子200突变和168 bp插入。为了检测朊病毒蛋白的精确定位，我们建立了一种新的预处理方法。称为水解高压灭菌。这种预处理可以揭示异常朊病毒蛋白在中枢神经系统灰质中的积累。这种弥漫性灰质染色在所有克雅氏病患者中均有记录。朊病毒蛋白免疫染色与突触素免疫染色相似。为了精确地检测，我们使用抗朊病毒蛋白和抗突触素进行了双重免疫标记。这两种免疫反应共定位于相同的突触结构。因此，我们报告 关于我们 在散发性Creutzfeldt-Jakob病患者中，异常朊蛋白的主要定位是突触结构。我们用水解高压灭菌增强法对朊蛋白多态性患者的组织切片进行了化学分析。朊病毒蛋白异常聚集可分为斑块形成（斑块型）和包括突触结构在内的弥漫性灰质染色（突触型）。插入多态性和密码子102、117/129、129的点突变均导致噬斑型朊病毒蛋白积聚。密码子102突变的患者也有突触型朊蛋白积聚。然而，密码子200的点突变没有显示空斑型积聚，而仅显示突触型朊蛋白积聚。同样，没有任何已知突变的散发性Creutzfeldt-Jakob病患者仅具有突触型累积。这些结果表明朊蛋白的一级结构影响朊蛋白病的表型，尤其是在中枢神经系统的异常朊蛋白分布中。少

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