An R5L τ mutation in a subject with a progressive supranuclear palsy phenotype

被引:148
作者
Poorkaj, P
Muma, NA
Zhukareva, V
Cochran, EJ
Shannon, KM
Hurtig, H
Koller, WC
Bird, TD
Trojanowski, JQ
Lee, VMY
Schellenberg, GD
机构
[1] GRECC, Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98195 USA
[2] Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA
[3] Loyola Univ, Med Ctr, Dept Pharmacol, Maywood, IL 60153 USA
[4] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[5] Rush Presbyterian St Lukes Med Ctr, Dept Pathol, Chicago, IL 60612 USA
[6] Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA
[7] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA
[8] Univ Miami, Dept Neurol, Miami, FL 33152 USA
[9] Univ Washington, Dept Neurol, Seattle, WA 98195 USA
[10] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA
关键词
D O I
10.1002/ana.10340
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
MAPT, the gene encoding tau, was screened for mutations in 96 progressive supranuclear palsy subjects. A point mutation ((R)5(L)) 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 (R)5(L) mutation causes a progressive supranuclear palsy phenotype, presumably by a gain-of-function mechanism.
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收藏
页码:511 / 516
页数:6
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