Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice
Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice
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DOI：
10.1016/s0304-3940(99)00964-7
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发表时间：
2000-02-04
影响因子：
2.5
通讯作者：
Hirokawa, N
中科院分区：
文献类型：
--
作者：
Ikegami, S;Harada, A;Hirokawa, N
Tau 是主要的神经元微管相关蛋白 (MAP) 之一，对于神经元细胞形态发生和轴突维持非常重要。 Tau 蛋白也是阿尔茨海默病患者体内成对螺旋丝 (PHF) 的组成部分。最近，在一种名为额颞叶痴呆和与 17 号染色体相关的帕金森病 (FTDP-17) 的遗传性神经退行性疾病中发现了 tau 基因突变，该疾病表现出各种神经学和神经病理学特征，包括类似 PHF 的细胞内 tau 沉积物形成。目前，该疾病的表型被认为是由于：（1）突变tau分子和/或的毒性； (2)患者大脑中正常tau分子功能丧失。为了检验后一个假设，我们对 tau 缺陷小鼠进行了行为和神经学测试。 Tau 缺陷小鼠在吊线测试中表现出肌肉无力、在新环境中表现出过度活跃以及情境恐惧条件反射受损。他们在走竿测试中也更容易跌倒。这些表型与 FTDP-17 患者的一些体征和症状相似。我们的结果表明，tau 蛋白的缺失本身可能会导致在 FTDP-17 患者中观察到的一些神经学特征。 (C) 2000 Elsevier Science Ireland Ltd. 保留所有权利。
Tau, one of the major neuronal microtubule-associated proteins (MAPs), is important for neuronal cell morphogenesis and axonal maintenance. Tau is also known to be a component of the paired helical filaments (PHFs) in Alzheimer's disease patients. Recently, mutations in the tau gene were found in a hereditary neurodegenarative disease called frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) which exhibits various neurological and neuropathological characteristics including PHF-like intracellular tau deposit formation. Currently, the phenotype of the disease is thought to be due to: (1) the toxicity of mutant tau molecules and and/or; (2) the loss of function of normal tau molecules in patients' brains. To test the latter hypothesis, we performed behavioral and neurological tests on tau-deficient mice. Tau-deficient mice showed muscle weakness in the wire-hanging test, hyperactivity in a novel environment, and impairment in the contextual fear conditioning. They also had a tendency to fall more easily in the rod-walking test. These phenotypes parallel some signs and symptoms of FTDP-17 patients. Our results show that the loss of tau protein may itself lead to some of the neurological characteristics observed in FTDP-17 patients. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.