Analysis of gene expression in Ca2+-dependent activator protein for secretion 2 (Cadps2) knockout cerebellum using GeneChip and KEGG pathways

Analysis of gene expression in Ca2+-dependent activator protein for secretion 2 (Cadps2) knockout cerebellum using GeneChip and KEGG pathways
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DOI:
10.1016/j.neulet.2016.12.068
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发表时间:
2017-02
影响因子:
2.5
通讯作者:
T. Sadakata;Y. Shinoda;Y. Ishizaki;T. Furuichi
T. Sadakata;Y. Shinoda;Y. Ishizaki;T. Furuichi
中科院分区:
医学4区
文献类型:
--
作者:
T. Sadakata;Y. Shinoda;Y. Ishizaki;T. Furuichi

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在小鼠小脑中,Ca 2+依赖性分泌激活蛋白2(CADPS 2,CAPS 2)参与调节致密核心囊泡(DCV)的分泌,DCV含有神经肽,包括脑源性神经营养因子(BDNF)和神经营养因子-3(NT-3)。为了了解Capds 2缺失所引起的分子影响,我们使用基因芯片微阵列和KEGG Pathway数据库分析了Capds 2KO小脑中的基因表达谱。在芯片上显示的22,690个基因中,有1211个(5.34%)观察到显著差异表达。胞吐相关基因(Stx 5a、Syt 6)、编码分泌蛋白(Fgf 2、Fgf 4、Edn 2)和突触蛋白(Grin 2b、Gabbr 1)的基因、神经营养因子信号相关基因(Sos 1、Shc 1、Traf 6、Psen 2)和Rett综合征基因(Mecp 2)的表达水平发生显著变化。总之,这些结果表明,由Capds 2缺失引起的基因表达失调可能导致发育缺陷和/或病理症状,导致自闭症样表型。
In the mouse cerebellum, Ca2+-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).Capds2knockout (KO) mice show impaired cerebellar development in addition to autistic-like behavioral phenotypes. To understand the molecular impact caused by loss ofCapds2, we analyzed gene expression profiles in theCapds2KO 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 ofCapds2may cause developmental deficits and/or pathological symptoms, resulting in autistic-like phenotypes.