Filamentous tau in oligodendrocytes and astrocytes of transgenic mice expressing the human tau isoform with the P301L mutation

Filamentous tau in oligodendrocytes and astrocytes of transgenic mice expressing the human tau isoform with the P301L mutation
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DOI:
10.1016/s0002-9440(10)63812-6
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发表时间:
2003-01-01
影响因子:
6
通讯作者:
Dickson, DW
Dickson, DW
中科院分区:
医学2区
文献类型:
--
作者:
Lin, WL;Lewis, J;Dickson, DW

文献摘要

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我们最近报道了一种转基因小鼠系(JNPL3),它表达突变体(P301L) tau,并产生由丝状tau聚集体组成的神经原纤维缠结。在这里,我们发现这些小鼠不仅在神经元中有异常的tau丝,而且在少突胶质细胞和星形胶质细胞中也有异常的tau丝。在另一个表达人类最长tau亚型P301L突变的转基因株系(JNPL2+3+)中也检测到类似的结果。在神经胶质细胞和神经元中,tau蛋白丝的超微结构以及对tau蛋白和泛素抗体的免疫反应性相似。鉴于小鼠病变与人类神经元和胶质包涵体的相似性,这些转基因小鼠似乎是研究神经退行性牛头病发病机制的有价值的模型。
We recently reported a transgenic mouse line (JNPL3) that expresses mutant (P301L) tau and develops neurofibrillary tangles composed of filamentous tau aggregates. Here we show that these mice have abnormal tau filaments not only in neurons, but also in oligodendrocytes and astrocytes. Similar results were detected in another transgenic line (JNPL2+3+) that expresses the longest human tau isoform with the P301L mutation. The ultrastructure of the tau filaments and immunoreactivity with tau and ubiquitin antibodies were similar in glia and neurons. Given similarities of the lesions in the mice to human neuronal and glial inclusions, these transgenic mice appear to be a valuable model to study pathogenesis of the neurodegenerative tauopathies.