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利用基因芯片和KEGG通路分析分泌型钙依赖性激活蛋白2(Cadps2)基因敲除小鼠小脑的基因表达情况。

Analysis of gene expression in Ca-dependent activator protein for secretion 2 (Cadps2) knockout cerebellum using GeneChip and KEGG pathways.

作者信息

Sadakata Tetsushi, Shinoda Yo, Ishizaki Yasuki, Furuichi Teiichi

机构信息

Advanced Scientific Research Leaders Development Unit, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.

Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.

出版信息

Neurosci Lett. 2017 Feb 3;639:88-93. doi: 10.1016/j.neulet.2016.12.068. Epub 2016 Dec 29.

Abstract

In the mouse cerebellum, Ca-dependent activator protein for secretion 2 (CADPS2, CAPS2) is involved in regulated secretion from dense-core vesicles (DCVs), which contain neuropeptides including brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). Capds2 knockout (KO) mice show impaired cerebellar development in addition to autistic-like behavioral phenotypes. To understand the molecular impact caused by loss of Capds2, we analyzed gene expression profiles in the Capds2 KO cerebellum using a GeneChip microarray and the KEGG Pathway database. Significant differential expression was observed in 1211 of 22,690 (5.34%) genes represented on the chip. The expression levels of exocytosis-related genes (Stx5a, Syt6), genes encoding secretory (Fgf2, Fgf4, Edn2) and synaptic proteins (Grin2b, Gabbr1), neurotrophin signaling-associated genes (Sos1, Shc1, Traf6, Psen2), and a gene for Rett syndrome (Mecp2) were significantly changed. Taken together, these results suggest that deregulated gene expression caused by loss of Capds2 may cause developmental deficits and/or pathological symptoms, resulting in autistic-like phenotypes.

摘要

在小鼠小脑中,钙依赖性分泌激活蛋白2(CADPS2,CAPS2)参与致密核心囊泡(DCV)的调节性分泌,致密核心囊泡包含包括脑源性神经营养因子(BDNF)和神经营养因子-3(NT-3)在内的神经肽。Capds2基因敲除(KO)小鼠除了具有自闭症样行为表型外,还表现出小脑发育受损。为了了解Capds2缺失所造成的分子影响,我们使用基因芯片微阵列和KEGG通路数据库分析了Capds2基因敲除小鼠小脑中的基因表达谱。在芯片上所代表的22,690个基因中的1211个(5.34%)基因中观察到了显著差异表达。胞吐相关基因(Stx5a、Syt6)、编码分泌蛋白(Fgf2、Fgf4、Edn2)和突触蛋白(Grin2b、Gabbr1)的基因、神经营养因子信号相关基因(Sos1、Shc1、Traf6、Psen2)以及雷特综合征相关基因(Mecp2)的表达水平发生了显著变化。综上所述,这些结果表明,Capds2缺失导致的基因表达失调可能会导致发育缺陷和/或病理症状,从而导致自闭症样表型。

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