Sadakata Tetsushi, Shinoda Yo, Ishizaki Yasuki, Furuichi Teiichi
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.
Neurosci Lett. 2017 Feb 3;639:88-93. doi: 10.1016/j.neulet.2016.12.068. Epub 2016 Dec 29.
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.
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。