Tau phosphorylation in transgenic mice expressing glycogen synthase kinase-3 beta transgenes
Tau phosphorylation in transgenic mice expressing glycogen synthase kinase-3 beta transgenes
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DOI：
10.1097/00001756-199710200-00013
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发表时间：
1997-10-20
期刊：
影响因子：
1.7
通讯作者：
Miller, CCJ
中科院分区：
文献类型：
--
作者：
Brownlees, J;Irving, NG;Miller, CCJ
为了研究在脑中操纵糖原合成酶激酶（GSK）-3 β活性对tau的影响，我们创建了携带野生型GSK-3 β基因或预测更活跃的突变GSK-3 β的转基因小鼠。在许多转基因小鼠品系的脑中检测到转基因衍生的mRNA，并且这些转基因品系中的一些表现出转基因GSK-3 β活性。对转基因GSK-3 β活性水平最高的两个系的蛋白质印迹分析显示，AT 8表位处tau的磷酸化状态升高。这些观察结果强烈表明GSK-3 β是脑中的体内tau激酶。仅获得低水平的GSK-3 β表达，并且高水平的GSK-3 β活性可能是致命的。
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.