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小鼠中神经元特异性缺失导致神经解剖学和运动缺陷。 (注:原文中“Neuron-Specific Deletion of in Mice”部分缺失具体内容,翻译可能不完全准确,需根据完整原文调整)

Neuron-Specific Deletion of in Mice Leads to Neuroanatomical and Locomotor Deficits.

作者信息

Ezan Jerome, Moreau Maité M, Mamo Tamrat M, Shimbo Miki, Decroo Maureen, Sans Nathalie, Montcouquiol Mireille

机构信息

INSERM U1215, Neurocentre Magendie, Bordeaux, France.

University of Bordeaux, Neurocentre Magendie, INSERM U1215, F-33000, Bordeaux, France.

出版信息

Front Genet. 2022 May 25;13:872700. doi: 10.3389/fgene.2022.872700. eCollection 2022.

Abstract

Scribble (Scrib) is a conserved polarity protein acting as a scaffold involved in multiple cellular and developmental processes. Recent evidence from our group indicates that is also essential for brain development as early global deletion of in the dorsal telencephalon induced cortical thickness reduction and alteration of interhemispheric connectivity. In addition, conditional knockout (cKO) mice have behavioral deficits such as locomotor activity impairment and memory alterations. Given broad expression in multiple cell types in the brain, we decided to determine the neuronal contribution of for these phenotypes. In the present study, we further investigate the function of specifically in excitatory neurons on the forebrain formation and the control of locomotor behavior. To do so, we generated a novel neuronal glutamatergic specific cKO mouse line called Nex cKO. Remarkably, cortical layering and commissures were impaired in these mice and reproduced to some extent the previously described phenotype in global cKO. In addition and in contrast to our previous results using cKO, the cKO mutant mice exhibited significantly reduced locomotion. Altogether, the novel cKO model described in this study further highlights an essential role for in forebrain development and locomotor behavior.

摘要

scribble(Scrib)是一种保守的极性蛋白,作为支架参与多种细胞和发育过程。我们小组最近的证据表明,它对大脑发育也至关重要,因为在背侧端脑早期全局缺失该蛋白会导致皮质厚度减少和半球间连接改变。此外,条件性敲除(cKO)小鼠存在行为缺陷,如运动活动受损和记忆改变。鉴于该蛋白在大脑多种细胞类型中广泛表达,我们决定确定其对这些表型的神经元贡献。在本研究中,我们进一步研究了该蛋白在兴奋性神经元中对前脑形成和运动行为控制的具体功能。为此,我们构建了一种名为Nex cKO的新型神经元谷氨酸能特异性cKO小鼠品系。值得注意的是,这些小鼠的皮质分层和连合受损,在一定程度上重现了之前在全局cKO中描述的表型。此外,与我们之前使用cKO的结果相反,cKO突变小鼠的运动明显减少。总之,本研究中描述的新型cKO模型进一步突出了该蛋白在前脑发育和运动行为中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5389/9174639/e4c7b727700a/fgene-13-872700-g001.jpg

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