Effects on splicing and protein function of three mutations in codon N296 of tau in vitro
Effects on splicing and protein function of three mutations in codon N296 of tau in vitro
复制标题
DOI：
10.1016/s0304-3940(02)00124-6
复制
发表时间：
2002-04-19
影响因子：
2.5
通讯作者：
Hutton, M
中科院分区：
文献类型：
--
作者：
Grover, A;DeTure, M;Hutton, M
最近报道了 tau 基因外显子 10 的同一密码子 (N296) 中的三个突变。其中两个突变 N296N 和 N296H 会导致类似于常染色体显性额颞叶痴呆伴 17 号染色体帕金森病的临床综合征。相比之下，第三个突变 delN296 在该突变纯合子个体中引起非典型进行性核上性麻痹，但在杂合子个体中，该突变是不完全外显的，并与类似于特发性麻痹的表型相关。帕金森病。采用功能测定来确定这些突变对外显子 10 选择性剪接、微管组装和重组 tau 蛋白自聚集的影响。我们证明这些突变表现出 tau 功能的一系列潜在致病性变化，并深入了解 delN296 突变不完全渗透表型的可能原因。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
Three Mutations were recently reported in the same codon (N296) in exon 10 of the tau gene. Two of these mutations, N296N and N296H, lead to a clinical syndrome similar to autosomal dominant fronto-temporal dementia with Parkinsonism linked to chromosome 17. In contrast the third mutation, delN296, gives rise to atypical progressive supranuclear palsy in individuals homozygous for the mutation, but in heterozygous individuals this mutation is incompletely penetrant and associated with a phenotype similar to idiopathic Parkinson's disease. Functional assays were employed to determine the effects of these mutations on alternative splicing of exon 10, on microtubule assembly and self-aggregation of recombinant tau protein. We demonstrate that these mutations exhibit a spectrum of potentially pathogenic changes in tau function, and provide insight into the possible cause of the incompletely penetrant phenotype of the delN296 mutation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.