调节GALR2基因关键转录因子的鉴定及其在抑郁中的作用

项目名称： 调节GALR2基因关键转录因子的鉴定及其在抑郁中的作用

项目编号： No.31271154

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 杨予涛

作者单位： 首都医科大学

项目金额： 76万元

中文摘要： 甘丙肽2型受体（GALR2）是神经肽甘丙肽的受体之一，广泛存在于中枢和外周组织。近年来的研究表明GALR2除了参与学习与记忆、神经再生、疼痛等重要的生理功能外，还参与抗抑郁的过程。尽管人们对GALR2受体的功能有了一定的了解，但影响其表达的转录因子及调控机制尚不清楚。本项目拟利用生物信息学、缺失分析、定点突变、EMSA和DNA decoy等方法鉴定影响大鼠GALR2基因表达的关键顺式作用元件，然后利用EMSA、ChIP和siRNA等技术确定调节GALR2基因表达的关键转录因子，最后再用动物行为学实验来研究调节GALR2基因表达的关键转录因子对抑郁模型动物的影响。本项目的研究不仅有助于阐明GALR2基因的表达调控机制，而且也有助于抑郁症治疗新靶点的发现。

中文关键词： GALR2；启动子；转录因子；抑郁；ETS-1

英文摘要： Galanin R2 receptor (GALR2), a member of neuropeptide galanin receptor family, is widely distributed in central and peripheral nervous systems. Recent studies have shown that GALR2 is involved in many important physiological functions, such as learning and memory, nerve regeneration, pain and etc. It has also been demonstrated that GALR2 plays an important role in depression. Although the role of GALR2 has been studied extensively,its transcriptional regulation mechanism is still unknown. In the present project: 1) the key cis-elements which regulate GALR2 gene expression will be identified using bioinformatics, deletion analysis, site mutation，DNA decoy and EMSA; 2) the key transcription factors will be determined by EMSA, ChIP and siRNA; and 3) the roles of those key transcription factors in animal model of depression will be investigated with animal behaviour experiments. Thus, this study may lead to understand the transcriptional regulation mechanism of GALR2 gene and provide a new clue for anti-depression therapy.

英文关键词： GALR2；promoter；transcriptional factor；depression；ETS-1