Mutations of glucocerebrosidase: discrimination of neurologic and non-neurologic phenotypes of Gaucher disease.
Mutations of glucocerebrosidase: discrimination of neurologic and non-neurologic phenotypes of Gaucher disease.
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葡萄糖脑苷脂酶突变：戈谢病神经学和非神经学表型的区分。
DOI：
10.1073/pnas.79.18.5607
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发表时间：
1982
影响因子：
11.1
通讯作者：
J. Barranger
中科院分区：
文献类型：
--
作者：
I. Edward;Ginns;R. O. Brady;Samuel Pirruccello;Carol Moore;Susan H. Sorrell;F. Furbish;Gary J. Murray;Joseph TAGERt;J. Barranger
已在成纤维细胞和人脑组织中通过放射免疫学鉴定出β-葡萄糖脑苷脂酶的多种分子形式，可区分戈谢病的神经学和非神经学表型。在正常人成纤维细胞中，这些形式已通过NaDodSO 4/聚丙烯酰胺凝胶电泳显示具有63，000（A1型）、61，000（A2型）和56，000（B型）的表观Mr。Mr 63，000型可能是Mr 56，000型的前身。非神经性戈谢病（1型）成纤维细胞和正常脑组织的特征在于它们仅含有一种主要的免疫反应性蛋白，即Mr 56，000形式。相比之下，神经戈谢病表型的成纤维细胞提取物和脑组织仅含有较高分子量的A1和A2型。这些数据和戈谢病所有变体中酶的低残留活性表明β-葡糖脑苷脂酶的突变是等位的，并涉及活性位点。
Multiple molecular forms of beta-glucocerebrosidase that permit discrimination between neurologic and non-neurologic phenotypes of Gaucher disease have been identified radioimmunologically in fibroblasts and human brain tissue. In normal human fibroblasts these forms have been shown by NaDodSO4/polyacrylamide gel electrophoresis to have apparent Mr of 63,000 (form A1), 61,000 (form A2), and 56,000 (form B). The Mr 63,000 form may be a precursor of the Mr 56,000 form. Non-neurologic Gaucher disease (type 1) fibroblasts and normal brain tissue are characteristic in that they contain only one major immunoreactive protein, the Mr 56,000 form. In contrast, fibroblast extracts and brain tissue from neurologic Gaucher disease phenotypes contain only the higher molecular weight forms A1 and A2. These data and the low residual activity of the enzyme in all the variants of Gaucher disease suggest that the mutations of beta-glucocerebrosidase are allelic and involve the active site.