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

我们检测了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。首先，我们报道了密码子102或密码子117的点突变与Gerstmann-Straussler综合征有关。我们还在Pron蛋白富含甘氨酸的重复部分发现了129密码子突变、200密码子突变和168bp的插入。为了检测蛋白的精确定位，我们建立了一种新的前处理方法。指定为水解式高压灭菌法。这种预处理可以揭示中枢神经系统灰质中异常的Prion蛋白积聚。这种弥漫性灰质染色在所有克雅氏病患者中都有记录。Prion蛋白免疫染色与突触素免疫染色相似。为了准确地检测，我们使用了抗Pron蛋白和抗突触素进行了双重免疫标记。两种免疫反应共同定位于相同的突触结构。因此，我们报告了…更重要的是，在散发性克雅病患者中，异常的Prion蛋白的主要定位是突触结构。我们用水解高压灭菌增强法检测了Prion蛋白多态患者的组织切片。蛋白异常聚集可分为斑块形成(斑块型)和弥漫性灰质染色，包括突触结构(突触类型)。102、117/129、129密码子的插入多态和点突变均可导致菌斑样蛋白积聚。密码子102突变的患者也有突触类型的蛋白积聚。但是，200密码子的一个点突变没有显示斑块型堆积，而只显示了突触类型的PrP蛋白堆积。同样，没有任何已知突变的散发性克雅病患者只有突触类型的堆积。这些结果表明，Prion蛋白的一级结构影响了Prion蛋白病的表型，特别是在中枢神经系统异常的Prion蛋白分布中。较少

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