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神经纤层蛋白 65 敲除小鼠基因表达变化的微阵列分析:对异常认知和情绪障碍的影响。

Microarray Analysis of Gene Expression Changes in Neuroplastin 65-Knockout Mice: Implications for Abnormal Cognition and Emotional Disorders.

机构信息

Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.

Department of Radiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.

出版信息

Neurosci Bull. 2018 Oct;34(5):779-788. doi: 10.1007/s12264-018-0251-5. Epub 2018 Jul 5.

Abstract

Neuroplastin 65 (Np65) is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout (KO) mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially-expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdh1, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.

摘要

神经纤层蛋白 65(Np65)是一种免疫球蛋白超家族细胞黏附分子,参与突触形成和可塑性。我们最近的研究表明,Np65 敲除(KO)小鼠表现出认知和情绪障碍异常。然而,其潜在机制尚不清楚。在这项研究中,我们通过微阵列分析发现 Np65-KO 小鼠中有 588 个差异表达的基因。RT-PCR 分析还显示与发育和突触结构相关的基因表达发生改变,如 Cdh1、Htr3a 和 Kcnj9。此外,Western blot 结果表明,Np65-KO 小鼠中参与发育的 Wnt 蛋白 Wnt-3 的表达减少。令人惊讶的是,MRI 和 DAPI 染色显示 Np65-KO 小鼠侧脑室体积显著减小。综上所述,这些发现表明 Np65 的缺失会影响基因表达,这可能导致大脑发育异常。这些结果为 Np65 缺失小鼠改变的大脑功能的机制提供了线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8114/6129239/8957708b5f09/12264_2018_251_Fig1_HTML.jpg

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