Partial Deletion of the MAPT Gene: A Novel Mechanism of FTDP-17

被引：33

作者：

Rovelet-Lecrux, Anne ^{[1
]}

Lecourtois, Magalie ^{[1
]}

Thomas-Anterion, Catherine ^{[2
]}

Le Ber, Isabelle ^{[3
]}

Brice, Alexis ^{[3
]}

Frebourg, Thierry ^{[1
]}

Hannequin, Didier ^{[1
]}

Campion, Dominique ^{[1
]}

机构：

[1] Fac Med, Inserm U614, F-76183 Rouen, France

[2] CHU, Dept Neurol, F-42055 St Etienne, France

[3] Univ Paris 06, INSERM, Hop La Salpetriere, UMR S679,AP HP, F-75013 Paris, France

来源：

HUMAN MUTATION | 2009年 / 30卷 / 04期

关键词：

MAPT; deletion; FTDP-17; MAP-1B; FAMILIAL FRONTOTEMPORAL DEMENTIA; TAU-PROTEIN; MICROTUBULE-BINDING; HYPERPHOSPHORYLATED TAU; ALZHEIMERS-DISEASE; MUTATIONS; CELLS; ISOFORMS; DEGENERATION; TAUOPATHIES;

D O I：

10.1002/humu.20979

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

A heterozygous genomic deletion removing exons 6 to 9 of the microtubule associated protein tau (MAPT) gene, predicting to result into a truncated protein lacking the first microtubule binding domain, was detected in a patient with frontotemporal dementia (FTD). Cell culture experiments showed that the truncated tau isoforms had a dramatic decrease in the normal binding to microtubules but acquired the ability to bind microtubule associated protein-1B (MAP-1B). This indicates that this tauopathy likely results both from a loss of function mechanism and from a deleterious gain of function by which cytoplasmic deleted forms of tau sequester another MAP. Both mechanisms could contribute to impair microtubule dynamics. (C) 2009 Wiley-Liss, Inc.

引用

页码：E591 / E602

页数：12

共 39 条

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