腺苷酸环化酶3对小鼠出生后嗅觉神经细胞发育的作用及其机制

项目名称： 腺苷酸环化酶3对小鼠出生后嗅觉神经细胞发育的作用及其机制

项目编号： No.31471178

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 王振山

作者单位： 河北大学

项目金额： 85万元

中文摘要： 主要嗅觉表皮(MOE)是哺乳动物的嗅觉器官?MOE内嗅觉神经细胞发生是一个终生持续的过程,对嗅觉行为具有重要影响?嗅觉神经细胞发生与细胞增殖和凋亡及DNA甲基化密切相关?腺苷酸环化酶3(AC3)是嗅觉神经细胞内cAMP信号通路的主要成分,敲除AC3基因的小鼠气味探测及嗅觉行为失常,其机制尚待明了?推测AC3敲除小鼠因感受气味刺激活动减弱导致嗅觉神经细胞发育缺陷,且AC3的功能可能因发育时期不同而异?为了明确AC3基因对嗅觉神经细胞发育的影响及其机制,本项目拟以不同发育时期AC3基因敲除及其野生小鼠MOE组织为材料,运用免疫荧光染色?原位杂交?DNA甲基化芯片及甲基化特异PCR等技术组合,鉴定AC3对小鼠出生后MOE内嗅觉神经细胞发育的作用,并对其发育缺陷的细胞增殖和凋亡及其DNA甲基化机制进行分析,旨在阐明AC3基因对嗅觉神经细胞发育的作用及其调控机理,为嗅觉健康诊断和药物研发提供依据。

中文关键词： 腺苷酸环化酶；嗅觉神经细胞；基因敲除小鼠；成年神经发生；DNA甲基化

英文摘要： The main olfactory epithelium (MOE) is the principal tissue for sensing odors in vertebrate. Olfactory receptor neuron (ORN) replacement in the MOE is a continuous process in lifelong. It plays important roles on olfactory behaviors in animals. The postnatal neurogenesis of ORN is sculpted by cell proliferation and programmed cell death (apoptosis), and is regulated by DNA methylation. Adenylyl cyclase 3 (AC3) is a key component of the cyclic adenosine-3'-5'-monophosphate (cAMP) signaling pathway within olfactory cilia of the ORNs in the MOE. Our previous works indicated that mice with deficiency of AC3 (AC3-/-) exhibit abnormally in odorant detections and correlative behaviors. However, the detailed underlying mechanisms are elusive. Neuronal activity is essential for survival of ORNs in a competitive environment. Therefore, we speculate that postnatal neurogenesis of ORNs might be impaired in AC3-/- mice, because neuronal activities evoked by odorants are dramatically decreased in the ORNs of these animals.Furthermore,the functions of AC3 on neurogenesis of ORNs might be different dependent on the developmental stages after postnatal. In the current proposal, the functions of AC3 on postnatal neurogenesis of ORNs, as well as its proliferative，apoptotic, and the underlying DNA methylation mechanisms will be investigated, by using technical combinations consisted of immunofluorescence staining, in-situ hybridization, DNA methylation microarray, and methylation-specific PCR and so on, with MOEs from different aged AC3-/- and AC3+/+ mice. The aim of this proposal is to characterize the effect of AC3 on neurogenesis of ORNs in postnatal mice, as well as its underlying mechanisms, in order to provide basis for olfactory diagnosis for our human health and the R&D of drugs.

英文关键词： adenylyl cyclase;olfactory receptor neuron;gene knockout mice;adult neurogenesis;DNA methylation