小鼠视神经发育损伤相关基因的凝聚性分层聚类分析

Hierarchical clustering the genes related to mouse optic nerve development and injury

目的对前期工作中采用高密度基因芯片技术筛选到的视神经发育、损伤相关基因进行聚类分析,以了解这些基因之间的相互联系,并根据已知功能和CNS轴突生长、导向相关的基因对部分未知功能基因进行功能预测.方法用Gene Cluster软件对筛选到的视神经发育、损伤相关基因进行凝聚性分层聚类,并对已知功能和CNS轴突生长、导向相关的Ptn、Efnb3所在的小组进行进一步的分析.结果 1 033个符合聚类条件的基因根据聚类的树型图分成6类,其中B类基因的表达模式和小鼠外侧膝状体的发育过程非常类似,它们可能是视神经发育的关键基因;5个功能完全未知的基因Mm.28443、Mm.9671、Mm.25504、Mm.160640、Mm.182895和Ptn基因聚类在同一个小组中,它们和Ptn基因的相关性非常高,Pearson相关系数为0.979～0.996,这些基因我们暂时作为神经轴突生长、导向相关的候选基因;Lamr1基因和Efnb3基因的相似性很高,结合文献,推测Lamr1及其配体是视神经发育的重要轴突导向分子.结论新的轴突导向因子的发现能为基因工程治疗CNS损伤提供潜在的靶基因.

Objective To find out the correlation genechips related to mice optic nerve development and tions of some unknown genes according to some genes among the genes which were screened by high density injury in our previous work, then to estimate the funcknown related to CNS neurite extention and guidance. Methods Hierarchical clustering method was applied for the genes mentioned above and the subgroups respectively containing Ptn, Efnb3 were further analyzed. Results A total of 1 033 suitable candidate genes were clustered into 6 groups. The gene expression pattern of group B was identical to the development pattern of lateral geniculate body （ LGN）, which supposed that the genes of group B might be the key genes to the optic never development. Five functionally unknown genes Mm. 28443, Mm. 9671, Mm. 25504, Mm. 160640, Mm. 182895 were clustered into a subgroup together with Ptn. The Pearson＇s coefficient between each of them and Ptn varied from 0. 979 to 0. 996. These genes were supposed to be candidate genes related to neurite growth and guidance. Lamrl and its ligand were assumed to be the neurite guiding molecules for optic never, both beacuse of its high Coefficient to Efnb3 gene and related documents. Conclusion New neurite guiding molecules might be potential target genes for CNS regeneration by genetic engineering.