维甲酸诱导腭裂小鼠的舌组织基因芯片筛选和差异基因生物学信息的初步探讨  

Analysis of gene expression and function in the tongue of retinoic acid-induced cleft palate by gene-chip technology

作　　者：王媛媛 刘波[2] 蒋玉玲[2,3] 丛蔚[2] 肖晶 WANG Yuan-yuan;LIU Bo;JIANG Yu-ling;CONG Wei;XIAO Jing(Dalian Stomatological Hospital,Liaoning Dalian 116021,China;Dalian Medical University,Liaoning Dalian 116044,China;The First People＇s Hospital of Xiangyang affiliated to Hubei Medical College,Hubei Xiangyang 441000,China.)

机构地区：[1]大连市口腔医院,辽宁大连116021 [2]大连医科大学,辽宁大连116044 [3]湖北医药学院附属襄阳市第一人民医院,湖北襄阳441000

出　　处：《临床口腔医学杂志》2018年第8期459-464,共6页Journal of Clinical Stomatology

基　　金：国家自然科学基金面上项目(81570962)

摘　　要：目的:利用基因芯片技术筛选维甲酸腭裂小鼠舌组织相关的差异基因,确定其功能及相关信号通路,并观察差异表达基因在维甲酸诱导腭裂小鼠形成中基因表达变化的调控模式及其生物学意义。方法:建立维甲酸诱导的腭裂小鼠模型,在ICR系小鼠怀孕第10 d管饲浓度为100 mg/kg全反式维甲酸,获取胚胎13.5 d的实验组和对照组小鼠舌组织,进行Affymetrix Mouse 430 2.0表达谱芯片实验,获得维甲酸腭裂小鼠的舌组织的异常表达基因,进而结合GO分类功能分析差异基因功能。通过Biocarta及Kegg信号通路数据库查询筛选基因相关转导信号通路信息,并分析在腭裂发生发展过程中信号转导以及基因表达调控网络等相关信息。结果:基于腭裂与舌组织基因表达谱芯片结果,以两倍差异倍数为标准筛选差异表达基因,共发现差异基因2146个,其中发现上调的基因有1457个,下调的基因689个。未被注释的631个,已经注释1515个。上调的差异基因功能大多与粘多糖生物合成过程、小脑发育、间充质细胞正调控以及肌动蛋白聚合或解聚有关。下调的基因功能大多与神经管的闭合、Wnt受体的正负调控、细胞增殖的调控和细胞外基质组成有关。主要的差异基因相应信号转导通路如Metabolic pathway,Hedgehog signaling pathway,Wnt signaling pathway,MAPK signaling pathway等可能在腭裂的发生发展中起重要作用。结论:利用基因芯片技术,在维甲酸诱导腭裂小鼠舌组织中发现了涉及到多个信号通路的上千个差异基因表达,提示舌发育异常可能直接导致腭裂发生。Objective： Gene chip technology was employed to screen the differentially genes expression of retinoic acid-induced cleft palate tongue tissue in mice. The function and its associated signal pathway were established to investigate the controlling mode of the gene expression changes and possible biological significance between the normal and retinoic acidinduced cleft palate mice. Methods： To establish acid-induced cleft palate mice model,all-trans RA（ 100 mg/kg） was given to E10 ICR pregnant mice,then obtain the experimental group and control group of mice tongue tissues from embryos of 13. 5 days to perform Affymetrix Mouse 430 2. 0 expression profiling chip experiment. Preliminary analysis of expression genes were further analyzed by the combination of the GO classification to distinguished the functions of differential genes. Signal pathway was screened by using signal transduction database of Bio Carta and Kegg,and signal transduction was further analyzed to study the related genes expression controlling network in the process of cleft palate. Results： Base on the results of expression profiling chip,using the 2-fold change cut off,differentially expressed genes were identified of 2146 with 1457 up-regulated and 689 down-regulated transcripts by using 2-fold change standard to screen the differential gene expression. Totally 631 gene expressions have not been annotated,and 1515 gene expressions have been annotated. The deferential function of upregulated genes were usually related to glycosaminoglycan biosynthetic process,cerebellum development,positive regulation of mesenchymal cell proliferation,actin polymerization or depolymerization. And down-regulated gens were usually related to the neural tube closure,Wnt receptor signaling pathway,extracellular matrix organization,positive regulation of cell proliferation.From the perspective of the signaling pathway,the major differences of genes obtained were the signal transduction pathway information,such as Metabolic pathways,Wnt Signaling Pathway,Hedg

关 键 词：维甲酸 腭裂 基因芯片 生物信息学分析 

分 类 号：R782[医药卫生—口腔医学]