摘要
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。
Objective To screen the genes related to the development and injury of central nervous system (CNS) for providing some suitable target genes applied for CNS injury repair by rational genetic engineering. Methods Gene expression was profiled by high density genechips in murine lateral geniculate bodies while optic nerves underwent 8 various stages of either development or injury. Results A total of 2 041 differentially expressed genes were found, including 1 095 highly expressed genes (ratio≥2) and 946 lowly expressed genes (ratio≤0.5). The 1095 highly expressed genes were classified into 17 groups according to their functions described by GENEBANK, GENEKARD, and SOURCE, such as transcription regulation, signal transduction, materials transporting, energy metablism, and so on. The largest two functional gene groups of development were transcript regulation and signal transduction, while the largest two of the injury were metabolism and material transduction. Some important genes facilitating to axon growth and guidance were only detected in the developmental period such as Efnb3, Ptn, Nrp, and Dbn1. Moreover, the expression of Rtn4, also called Nogo-A, which is the strongest blocking factor to axon extention of Nogo family, was found only in the injured groups. Nevertheless, Mdk, another key gene related to neuron migration and neurite growth, was found in both the developmental and injured groups. Conclusion These genes might be the key genes in the progression of optic nerve development and injury repair.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2004年第24期2218-2222,共5页
Journal of Third Military Medical University
基金
全军医学科学技术研究"十五"计划基金重点课题 ( 0 1Z0 6 8)~~
关键词
基因芯片
中枢神经系统
损伤
发育
genechip
central nervous system
development
injury