Poorkaj Parvoneh, Muma Nancy A, Zhukareva Victoria, Cochran Elizabeth J, Shannon Kathleen M, Hurtig Howard, Koller William C, Bird Thomas D, Trojanowski John Q, Lee Virginia M-Y, Schellenberg Gerard D
Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA 98195, USA.
Ann Neurol. 2002 Oct;52(4):511-6. doi: 10.1002/ana.10340.
MAPT, the gene encoding tau, was screened for mutations in 96 progressive supranuclear palsy subjects. A point mutation (R5L) was identified in a single progressive supranuclear palsy subject that was not in the other progressive supranuclear palsy subjects or in 96 controls. Functionally, this mutation alters the ability of tau to promote microtubule assembly. Analysis of soluble tau from different brain regions indicates that the mutation does not affect the ratio of tau isoforms synthesized. Aggregated insoluble tau from subcortical regions was predominantly four-repeat tau with no or one amino terminal insert (0N4R and 1N4R). Insoluble tau from cortical regions also contained 1N3R tau. Thus, the R5L mutation causes a progressive supranuclear palsy phenotype, presumably by a gain-of-function mechanism.
对96名进行性核上性麻痹患者进行了编码tau的基因MAPT的突变筛查。在一名进行性核上性麻痹患者中发现了一个点突变（R5L），该突变在其他进行性核上性麻痹患者或96名对照中均未出现。从功能上来说，这种突变改变了tau促进微管组装的能力。对来自不同脑区的可溶性tau的分析表明，该突变不影响所合成的tau异构体的比例。来自皮质下区域的聚集性不溶性tau主要是四重复tau，没有或有一个氨基末端插入片段（0N4R和1N4R）。来自皮质区域的不溶性tau也含有1N3R tau。因此，R5L突变可能通过功能获得机制导致进行性核上性麻痹表型。
