精神分裂症易感基因GNA13功能的初步分析

Preliminary functional analysis of schizophrenia susceptibility gene GNA13

目的初步分析G蛋白α亚基13(GNA13)基因在精神分裂症中的作用,探索精神分裂症发病机制的相关生物通路。方法用出生24 h内的C57BL6N野生型幼鼠进行大脑皮层原代神经元细胞培养,使用重组病毒感染并敲低实验组的Gna13基因,空载病毒感染空载对照组,对照组不做任何干预,在同等条件下继续培养。3组均进行蛋白和mRNA表达水平测定,用高通量测序技术检测其mRNA表达谱,并进行Phenotype表型富集、Kyoto encyclopedia of gene and genomes(KEGG)通路富集、gene ontology(GO)功能富集分析。结果与对照组相比,实验组中存在差异性表达的基因共211个(P<0.05,FDR校正),其中表达上调基因141个,表达下调基因70个。表达下调基因主要与异常有丝分裂、脑形态异常、产前发育迟缓等表型相关,与细胞代谢、细胞周期的催化调节、细胞蛋白质定位等生物过程相关,与细胞周期、代谢途径以及肌动蛋白细胞骨架的调节和粘附力等生物通路相关。结论 GNA13基因可能通过影响神经细胞形态和突触可塑性构成,参与精神分裂症的发生发展。

Objective To analyze the function of the GNA13 gene in schizophrenia and find some related biological pathways of pathogenesis.Methods C57 BL6 N wild-type mice born within 24 h were used to culture the primary neuronal cells of the cerebral cortex.The cells were transfected with recombinant virus carrying siRNA for knockdown of Gna13 gene in the experimental group.The empty control group was infected empty-load virus and the control group didn’t receive any intervention.The levels of protein and mRNA expression levels were examined in all the groups.The mRNA expression profiles were detected by high-throughput sequencing technology, followed by the bioinformatic analysis.Results Compared with the control group, there were 211 differentially expressed genes in the infected group(P<0.05), False Discovery Rate(FDR) corrected, including 141 genes with up-regulated expression and 70 genes with down-regulated expression.Down-regulated genes were mainly associated with phenotypes such as abnormal mitosis, abnormal brain morphology, and prenatal growth retardation;associated with biological processes such as cellular metabolic process, positive regulation of cell cycle, and cellular protein localization;associated with KEGG pathway such as cell cycle, metabolic pathways, focal adhesion and regulation of actin cytoskeleton.Conclusion GNA13 gene may be involved in the formation of the morphology of neuronal cell and the plasticity of synaptic, which may in turn cause the development of schizophrenia.