Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau
Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau
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DOI：
10.1523/jneurosci.22-01-00133.2002
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发表时间：
2002-01-01
影响因子：
5.3
通讯作者：
Takashima, A
中科院分区：
文献类型：
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作者：
Tanemura, K;Murayama, M;Takashima, A
神经原纤维缠结（NFT）的形成是多种神经退行性疾病（包括阿尔茨海默病）中常见的神经病理学特征。我们开发了一种表达突变型人类 tau (V337M) 的转基因 (Tg) 小鼠，该突变源自额颞叶痴呆帕金森症 17。 V337M Tg 小鼠在海马体中发现 tau 蛋白聚集，这符合人类神经退行性疾病中 NFT 的组织学标准。在RNA和磷酸化tau蛋白积累的同时，神经元表现出退化神经元的形态特征，包括微管损失、核糖体积累、质膜和核膜皱褶以及高尔基体网络肿胀。因此，突变的 tau 蛋白会诱导与 RNA 和磷酸化 tau 蛋白积累相关的神经元变性。 Tg 小鼠海马神经活动减少和行为异常证明了这种神经元变性的功能后果。
Formation of neurofibrillary tangles (NFTs) is a common neuropathological feature found in several neurodegenerative diseases, including Alzheimer's disease. We have developed a transgenic (Tg) mouse expressing mutant human tau (V337M), derived from frontotemporal dementia parkinsonism-17. V337M Tg mice revealed tau aggregations in the hippocampus, which fulfills the histological criteria for NFTs in human neurodegenerative diseases. Concurrent with the accumulation of RNA and phosphorylated tau, neurons exhibited morphological characteristics of degenerating neurons, which include a loss of microtubules, accumulation of ribosomes, plasma and nuclear membrane ruffling, and swelling of the Golgi network. Thus, mutant tau induces neuronal degeneration associated with the accumulation of RNA and phosphorylated tau. The functional consequences of this neuronal degeneration was evidenced by the reduction of hippocampal neural activity and behavioral abnormality in Tg mice.