Identification of HE1 as the second gene of Niemann-Pick C disease
Identification of HE1 as the second gene of Niemann-Pick C disease
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DOI：
10.1126/science.290.5500.2298
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发表时间：
2000-12-22
期刊：
影响因子：
56.9
通讯作者：
Lobel, P
中科院分区：
文献类型：
--
作者：
Naureckiene, S;Sleat, DE;Lobel, P
C2型尼曼-匹克病（NP-C2）是一种病因不明的致死性遗传性疾病，其特征是胆固醇从溶酶体中排出缺陷。在这里，我们表明，这种疾病是由缺乏HE 1，一种普遍表达的溶酶体蛋白，以前确定为胆固醇结合蛋白。在NP-C2患者的成纤维细胞中检测不到HE 1，但在未受影响的对照和NP-C1患者的成纤维细胞中存在HE 1。定位于染色体14q24.3的HE 1基因突变在NP-C2患者中发现，但在对照组中未发现。用外源性重组HE 1蛋白处理NP-C2成纤维细胞可改善低密度脂蛋白衍生胆固醇的溶酶体蓄积。
Niemann-Pick type C2 disease (NP-C2) is a fatal hereditary disorder of unknown etiology characterized by defective egress of cholesterol from lysosomes. Here we show that the disease is caused by a deficiency in HE1, a ubiquitously expressed lysosomal protein identified previously as a cholesterol-binding protein. HE1 was undetectable in fibroblasts from NP-C2 patients but present in fibroblasts from unaffected controls and NP-C1 patients. Mutations in the HE1 gene, which maps to chromosome 14q24.3, were found in NP-C2 patients but not in controls. Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.