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Pathological study of mutant SOD1 (G93A and H46R) transgenic mice

突变型SOD1（G93A和H46R）转基因小鼠的病理研究

基本信息

批准号：
14570623
负责人：
SASAKI Shoichi
金额：
$ 2.18万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570623/
关键词：
amyotrophic lateral sclerosis SOD1 mutant SOD1 transgenic mice axonal transport mitochondria aggregate electron microscopy immuno-electron microscopy SOD1変異 G93A変異SOD1導入マウス aggregates 運動ニューロン疾患変異マウス超微細構造 G93A SOD1変異マウス軸索 /

项目摘要

We electronmicroscopically and immunoelectronmicroscopically investigated the spinal cords of transgenic(Tg) mice with a G93A mutant SOD1 gene to elucidate the pathomechanisms of this animal model for familial ALS.(1)Proximal axons directly emanating from normal-looking anterior horn cells with increased neurofilaments or, to a lesser extent, increased mitochondria, were more frequently observed in Tg mice than in the controls, even at the early presymptomatic stage, and the frequency increased with time. The somata of motor neurons directly connected with proximal axons did not exhibit any abnormal accumulation of neurofilaments or mitochondria.(2)Vacuoles of various sizes were observed in the anterior root exit zone, anterior root, and in the neuropils of the anterior horn. The intermembrane space of mitochondria was frequently vacuolated. In mitochodria with advanced vacuolation, the vacuolar space was filled with a granular or amorphous substance. Both SOD1 and ubiquitin determinants were localized in vacuolated mitochondria. The vacuolated mitochondria were exclusively observed in the axons, and not in proximal dendrites or somata.(3)SOD1-and ubiquitin-positive aggregates and Lewy body-like inclusions were frequently demonstrated in the neuronal processes including cord-like swollen axons and in some remaining anterior horn neurons in Tg mice. The aggregates increased in size and frequency with time. The aggregates almost always consisted basically of interwoven intermediate filaments (about 10-15 nm in diameter), showing a high level of human SOD1-and ubiquitin-immunogold labeling. Aggregates were frequently shown, predominating in the neuronal processes of the anterior horns including the proximal axons, whereas they were rather rare in the somata and dendrites.Thus, impairment of proximal axonal transport may play a pivotal role in the pathomechanism of this model.

我们通过电子显微镜和免疫电子显微镜研究了带有 G93A 突变 SOD1 基因的转基因（Tg）小鼠的脊髓，以阐明该动物模型的家族性 ALS 的病理机制。（1）近端轴突直接源自外观正常的前角细胞，神经丝增加，或者在较小程度上线粒体增加，即使在症状出现的早期阶段，Tg 小鼠中也比对照组小鼠更频繁地观察到这种现象，并且频率随着时间的推移而增加。与近端轴突直接相连的运动神经元体体未见神经丝或线粒体异常堆积。(2)前根出口区、前根、前角神经毡内可见大小不等的空泡。线粒体的膜间隙经常出现空泡。在具有高级空泡化的线粒体中，空泡空间充满颗粒状或无定形物质。 SOD1 和泛素决定簇均位于空泡线粒体中。空泡线粒体仅在轴突中观察到，而不是在近端树突或体细胞中观察到。(3)SOD1和泛素阳性聚集体和路易体样内含物经常出现在Tg小鼠的神经元突起中，包括索状肿胀的轴突和一些剩余的前角神经元中。聚集体的大小和频率随着时间的推移而增加。聚集体几乎总是由交织的中间丝（直径约 10-15 nm）组成，显示出高水平的人类 SOD1 和泛素免疫金标记。聚集体经常出现，主要存在于包括近端轴突在内的前角神经元过程中，而在体细胞和树突中则相当罕见。因此，近端轴突运输的损伤可能在该模型的病理机制中发挥关键作用。

项目成果

期刊论文数量（54）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ultrastructural study of aggregates in the spinal cord of transgenic mice with a G93A mutant SOD1 gene

DOI：
10.1007/s00401-004-0939-7
发表时间：
2005-03
期刊：
Acta Neuropathologica
影响因子：
12.7
作者：
S. Sasaki;H. Warita;T. Murakami;N. Shibata;T. Komori;K. Abe;Makio Kobayashi;M. Iwata
通讯作者：
S. Sasaki;H. Warita;T. Murakami;N. Shibata;T. Komori;K. Abe;Makio Kobayashi;M. Iwata

Ultrastructural study of mitochondria in the spinal cord of transgenic mice with a G93A mutant SOD1 gene