Expression of Kruppel-like factor 5 gene in human brain and association of the gene with the susceptibility to schizophrenia
Expression of Kruppel-like factor 5 gene in human brain and association of the gene with the susceptibility to schizophrenia
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DOI：
10.1016/j.schres.2007.11.042
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发表时间：
2008-03
影响因子：
4.5
通讯作者：
M. Yanagi;T. Hashimoto;N. Kitamura;M. Fukutake;O. Komure;N. Nishiguchi;T. Kawamata;K. Maeda;O. Shirakawa
中科院分区：
文献类型：
--
作者：
M. Yanagi;T. Hashimoto;N. Kitamura;M. Fukutake;O. Komure;N. Nishiguchi;T. Kawamata;K. Maeda;O. Shirakawa
利用DNA微阵列技术进行全基因组基因表达分析是寻找对精神分裂症易感的意外基因的潜在工具。我们在死后的前额叶皮质进行了基因芯片分析，发现KLF5基因在精神分裂症患者中的表达下调，该基因位于13q21上。这一结果得到了蛋白质印迹分析的证实。在一项遗传学研究中，我们发现KLF5基因(−1593T>；C)的一个多态性与精神分裂症有关。我们通过原位杂交和免疫组织化学的方法确定了人脑前额叶皮质的神经元是KLF5表达的部位。KLF5免疫组织化学定位于海马区的颗粒细胞和锥体细胞，它们是谷氨酸能神经传递的主要来源。这些结果提示KLF5基因是一个新的精神分裂症易感基因，该基因的表达可能通过谷氨酸能神经传递参与了精神分裂症的病理生理过程。
Genome-wide gene expression analysis using DNA microarray technology is a potential tool to search for unexpected genes that have a susceptibility to schizophrenia. We carried out a microarray analysis in the postmortem prefrontal cortex and found that the expression of the KLF5 gene, whose locus is on 13q21, was down-regulated in schizophrenia patients. This result was confirmed by a Western blot analysis. In a genetic study, we found that a polymorphism of the KLF5 gene (−1593T>C) was associated with schizophrenia. We identified neurons in the prefrontal cortex of human brain as sites of KLF5 expression by in situ hybridization and immunohistochemistry. KLF5 was immunohistochemically localized in granular and pyramidal cells in the hippocampus, which are the principal source of glutamatergic neurotransmission. These findings suggest that the KLF5 gene is a novel schizophrenia-susceptibility gene, and that the expression of the gene is involved in the pathophysiology of schizophrenia via glutamatergic neurotransmission.