Tau phosphorylation in transgenic mice expressing glycogen synthase kinase-3 beta transgenes

被引：87
作者：
Brownlees, J
Irving, NG
Brion, JP
Gibb, BJM
Wagner, U
Woodgett, J
Miller, CCJ
机构：
[1] INST PSYCHIAT,DEPT NEUROSCI,LONDON SE5 8AF,ENGLAND
[2] INST PSYCHIAT,DEPT CLIN NEUROSCI,LONDON SE5 8AF,ENGLAND
[3] INST PSYCHIAT,DEPT PSYCHOL,LONDON SE5 8AF,ENGLAND
[4] FREE UNIV BRUSSELS,LAB ANAT & MICROSCOPIE ELECT,B-1070 BRUSSELS,BELGIUM
[5] PRINCESS MARGARET HOSP,ONTARIO CANC RES INST,TORONTO,ON M5G 2M9,CANADA
来源：
NEUROREPORT | 1997年 / 8卷 / 15期
基金：
英国惠康基金;
关键词：
Alzheimer's disease; GSK-3; beta; phosphorylation; tau; transgenic mice;
D O I：
10.1097/00001756-199710200-00013
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
IN order to investigate the effect on tau of manipulating glycogen synthase kinase (GSK)-3 beta activity in the brain, we created transgenic mice harbouring wild-type GSK-3 beta genes or a mutant GSK-3 beta that is predicted to be more active. Transgene-derived mRNAs were detected in the brains of a number of the transgenic mouse lines and several of these transgenic lines displayed transgenic GSK-3 beta activity. Western blot analyses of the two lines with the highest levels of transgenic GSK-3 beta activity revealed that the phosphorylation status of tau was elevated at the AT8 epitope. These observations strongly suggest that GSK-3 beta is an in vivo tau kinase in the brain. Only low levels of expression of GSK-3 beta were obtained and it is possible that high levels of GSK-3 beta activity are lethal.
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收藏
页码：3251 / 3255
页数：5
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