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小脑颗粒神经元特异性敲除Golli-MBP小鼠的构建与鉴定

Generation and characterization of cerebellar granule neurons specific knockout mice of Golli-MBP.

作者信息

Miyazaki Haruko, Nishioka Saki, Yamanaka Tomoyuki, Abe Manabu, Imamura Yukio, Miyasaka Tomohiro, Kakuda Nobuto, Oohashi Toshitaka, Shimogori Tomomi, Yamakawa Kazuhiro, Ikawa Masahito, Nukina Nobuyuki

机构信息

Laboratory of Structural Neuropathology, Graduate School of Brain Science, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe-shi, Kyoto, 610-0394, Japan.

Department of Molecular Biology and Biochemistry, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.

出版信息

Transgenic Res. 2024 Jun;33(3):99-117. doi: 10.1007/s11248-024-00382-0. Epub 2024 Apr 29.

DOI:10.1007/s11248-024-00382-0
PMID:38684589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11176102/
Abstract

Golli-myelin basic proteins, encoded by the myelin basic protein gene, are widely expressed in neurons and oligodendrocytes in the central nervous system. Further, prior research has shown that Golli-myelin basic protein is necessary for myelination and neuronal maturation during central nervous system development. In this study, we established Golli-myelin basic protein-floxed mice to elucidate the cell-type-specific effects of Golli-myelin basic protein knockout through the generation of conditional knockout mice (Golli-myelin basic proteins; E3CreN), in which Golli-myelin basic proteins were specifically deleted in cerebellar granule neurons, where Golli-myelin basic proteins are expressed abundantly in wild-type mice. To investigate the role of Golli-myelin basic proteins in cerebellar granule neurons, we further performed histopathological analyses of these mice, with results indicating no morphological changes or degeneration of the major cellular components of the cerebellum. Furthermore, behavioral analysis showed that Golli-myelin basic proteins; E3CreN mice were healthy and did not display any abnormal behavior. These results suggest that the loss of Golli-myelin basic proteins in cerebellar granule neurons does not lead to cerebellar perturbations or behavioral abnormalities. This mouse model could therefore be employed to analyze the effect of Golli-myelin basic protein deletion in specific cell types of the central nervous system, such as other neuronal cells and oligodendrocytes, or in lymphocytes of the immune system.

摘要

由髓鞘碱性蛋白基因编码的Golli-髓鞘碱性蛋白在中枢神经系统的神经元和少突胶质细胞中广泛表达。此外,先前的研究表明,Golli-髓鞘碱性蛋白在中枢神经系统发育过程中的髓鞘形成和神经元成熟中是必需的。在本研究中,我们建立了Golli-髓鞘碱性蛋白floxed小鼠,通过生成条件性敲除小鼠(Golli-髓鞘碱性蛋白;E3CreN)来阐明Golli-髓鞘碱性蛋白敲除的细胞类型特异性效应,在这种小鼠中,Golli-髓鞘碱性蛋白在小脑颗粒神经元中被特异性删除,而在野生型小鼠中Golli-髓鞘碱性蛋白在小脑颗粒神经元中大量表达。为了研究Golli-髓鞘碱性蛋白在小脑颗粒神经元中的作用,我们进一步对这些小鼠进行了组织病理学分析,结果表明小脑的主要细胞成分没有形态变化或退化。此外,行为分析表明,Golli-髓鞘碱性蛋白;E3CreN小鼠健康,没有表现出任何异常行为。这些结果表明,小脑颗粒神经元中Golli-髓鞘碱性蛋白的缺失不会导致小脑紊乱或行为异常。因此,该小鼠模型可用于分析Golli-髓鞘碱性蛋白缺失在中枢神经系统特定细胞类型中的作用,如其他神经元细胞和少突胶质细胞,或免疫系统的淋巴细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e9/11176102/9c59a9187d43/11248_2024_382_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e9/11176102/60b4d127f990/11248_2024_382_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e9/11176102/a65052508409/11248_2024_382_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e9/11176102/12d02a8fa151/11248_2024_382_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63e9/11176102/acbbb94c1123/11248_2024_382_Fig4_HTML.jpg
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