应用高密度基因芯片筛选中枢神经系统发育和损伤相关基因的研究

来源 :第三军医大学学报 | 被引量 : 0次 | 上传用户:zhangyongqiangis250
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目的 探讨中枢神经系统 (CNS)发育、损伤相关基因 ,为基因工程治疗CNS损伤提供以一些可能的靶基因。方法 采用高密度的发育表达谱基因芯片 ,检测了在视神经发育、损伤共 8个不同的时相点上视神经的第一级投射站———外侧膝状体的基因表达情况。结果 以正常成年小鼠作为对照 ,共找到差异表达基因 2 0 41个 :高表达 (ratio≥ 2 )的基因 10 95个 ,其中在发育期间高表达的基因 5 60个 ,在损伤后高表达的基因 416个 ,在发育期间和损伤后均有高表达的基因119个 ;低表达 (ratio≤ 0 5 )的基因 946个 ,其中在发育期间低表达的基因 2 75个 ,在损伤后低表达的基因 45 8个 ,在发育期间和损伤后均有低表达的基因 2 13个。对高表达的 10 95个基因进行了功能检索、分组 ,共分为转录调节、信号转导、代谢和物质转运等 17组 ,其中在发育阶段数量最多的功能组是转录调节组和信号转导组 ,在损伤过程数量最多的功能组是代谢组和物质转运组。一些和轴突生长、导向、突触形成相关的基因Efnb3、Ptn、Nrp、Dbn1只在发育期间表达 ,抑制轴突生长的基因Rtn4只在损伤后表达 ,一个和神经元的迁移、轴突的生长相关的基因———Mdk在发育和损伤过程中均有高表达。结论 上述这些基因可能是视神经发育以及损伤、修复过程中起关键作 Objective To investigate the genes involved in the development and injury of the central nervous system (CNS), and to provide some possible target genes for genetic engineering treatment of CNS injury. Methods High-density gene expression profiling was used to detect the gene expression of the lateral geniculate body, the first level projection site of optic nerve in 8 different time points of optic nerve development and injury. RESULTS: A total of 21041 differentially expressed genes were found in normal adult mice: 10 95 genes were highly expressed (ratio ≥ 2), of which 5 60 were highly expressed during development and were highly expressed after injury There were 416 genes highly expressed during and after development, 946 genes were highly expressed (ratio≤0 5), of which 2 75 were low-expression genes during development. After low expression There were 458 genes with low expression of 2 13 during and after development. The high expression of 1095 genes were functional search, grouping, divided into 17 groups of transcriptional regulation, signal transduction, metabolism and substance transport, in which the most functional groups in the developmental stage is the transcriptional regulation group and signal transduction In the group, the functional groups with the largest number of injury processes were the metabolome and the substance transporter. Some genes involved in axonal growth, orientation and synapse formation, Efnb3, Ptn, Nrp, and Dbn1, are expressed only during development. Rtn4, a gene that inhibits axonal growth, is expressed only after injury, and is associated with neuronal migration, axonal Mdk, a growth-related gene, is highly expressed during development and injury. Conclusion These genes may be optic nerve development and injury, repair process plays a key role
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