小脑颗粒神经元特异性Golli-MBP基因敲除小鼠的产生和特征描述

IF 2.7 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Transgenic Research Pub Date : 2024-04-29 DOI:10.1007/s11248-024-00382-0
Haruko Miyazaki, Saki Nishioka, Tomoyuki Yamanaka, Manabu Abe, Yukio Imamura, Tomohiro Miyasaka, Nobuto Kakuda, Toshitaka Oohashi, Tomomi Shimogori, Kazuhiro Yamakawa, Masahito Ikawa, Nobuyuki Nukina
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摘要

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-髓鞘碱性蛋白是中枢神经系统发育过程中髓鞘化和神经元成熟所必需的。在本研究中,我们通过产生条件性基因敲除小鼠(Golli-myelin basic proteinsfl/fl; E3CreN),在小脑颗粒神经元中特异性地缺失Golli-髓鞘碱性蛋白,以阐明Golli-髓鞘碱性蛋白基因敲除对细胞类型的特异性影响。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发生形态变化或退化。此外,行为分析表明,Golli-髓鞘碱性蛋白fl/fl; E3CreN小鼠身体健康,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,这种小鼠模型可用于分析中枢神经系统特定细胞类型(如其他神经元细胞和少突胶质细胞)或免疫系统淋巴细胞中Golli-髓鞘碱性蛋白缺失的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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 (Gollimyelin basic proteinsfl/fl; 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 Gollimyelin basic proteinsfl/fl; 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.

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来源期刊
Transgenic Research
Transgenic Research 生物-生化研究方法
CiteScore
5.40
自引率
0.00%
发文量
38
审稿时长
4-8 weeks
期刊介绍: Transgenic Research focusses on transgenic and genome edited higher organisms. Manuscripts emphasizing biotechnological applications are strongly encouraged. Intellectual property, ethical issues, societal impact and regulatory aspects also fall within the scope of the journal. Transgenic Research aims to bridge the gap between fundamental and applied science in molecular biology and biotechnology for the plant and animal academic and associated industry communities. Transgenic Research publishes -Original Papers -Reviews: Should critically summarize the current state-of-the-art of the subject in a dispassionate way. Authors are requested to contact a Board Member before submission. Reviews should not be descriptive; rather they should present the most up-to-date information on the subject in a dispassionate and critical way. Perspective Reviews which can address new or controversial aspects are encouraged. -Brief Communications: Should report significant developments in methodology and experimental transgenic higher organisms
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