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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
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摘要 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.
作者 罗艺苹 刘可智 喻明兰 梁雪梅 张涛 向波 LUO Yiping;LIU Kezhi;YU Minglan;LIANG Xuemei;ZHANG Tao;XIANG Bo(Department of Psychiatry,Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)
出处 《中国神经精神疾病杂志》 CAS CSCD 北大核心 2019年第9期545-551,共7页 Chinese Journal of Nervous and Mental Diseases
基金 四川省卫健委科技项目(编号:18PJ310) 泸州市科技局项目(编号:2017-S-40(4/18)) 泸州市-西南医科大联合项目(编号:2016LZXNYD-T08,2017LZXNYD-Z02) 四川省教育厅重点项目(编号:18ZA0534) 西南医科大学附属医院青年项目(编号:17154)
关键词 精神分裂症 GNA13 基因 高通量核苷酸测序 基因表达 Schizophrenia GNA13 High-throughput Nucleotide sequencing Gene expression
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  • 1Schultz SK, Andreasen NC. Schizophrenia [J]. Lancet, 1999, 353 (9162):1425-1430.
  • 2Xie L, Ye L, Ju G, et al. A family and population-based study of the UFD1L gene for schizophrenia [J]. Am J Med Genet B Neuropsychiatr Genet, 2008, 147B (7): 1076- 1079.
  • 3Schwab SG, Wildenauer DB. Chromosome 22 workshop report [J]. Am J Med Genet, 1999, 88 (3): 276-278.
  • 4Mukai J, Dhilla A, Drew LJ, et al. Palmitoylation- dependent neurodevelopmental deficits in a mouse model of 22q11 mierodeletion [ J ]. Nat Neurosci, 2008, 11 (11): 1302-1310.
  • 5Gothelf D, Schaer M, Eliez S. Genes, brain development and psychiatric phenotypes in velo-cardio-facial syndrome [J]. Dev Disabil Res Rev, 2008, 14 (1): 59-68.
  • 6McIntosh AM, Baig BJ, Hall J, et al. Relationship of catechol-O-methyhransferase variants to brain structure and function in a population at high risk of psychosis [J]. Biol Psychiatry, 2007, 61 (10): 1127-1134.
  • 7Murphy KC. Schizophrenia and velo-cardio-facial syndrome [J]. Lancet, 2002, 359 (9304): 426-430.
  • 8Mukai J, Liu H, Burt RA, et al. Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia[J]. Nat Genet, 2004, 36: 725-731.
  • 9Condra JA, Neibergs H, Wei W, et al. Evidence for two schizophrenia susceptibility genes on chromosome 22q13 [J]. Psychiatr Genet, 2007, 17 (5) : 292-298.
  • 10沈文龙,李晨虎,饶顺曾,占归来,张红.精神分裂症患者伴发代谢综合征的患病率调查[J].神经疾病与精神卫生,2007,7(6):431-433. 被引量:41

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