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Analysis of human D2 dopamine receptor gene in schizophrenia

精神分裂症人D2多巴胺受体基因分析

基本信息

批准号：
02454291
负责人：
KUWANO Ryozo
金额：
$ 4.03万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454291/
关键词：
D2 dopamine receptor Gene Schizophrenia Polymorphism SSCP SSCP法ド-パミンD_2受容体

项目摘要

Dopamine and dopamine receptors may be involved in the movement and emotion balances. D2 dopamine receptor has high affinity for the antipsychotic drugs. Tliis receptor may also be related to the pathoctlenesis of Parkinson's disease and schizophrenia. We purified the bovine brain D2 dopamine receptor protein by photoaffinity labeling, high performance liquid chrom-atoaraphy and preparative sodium dodecyl sulphate polyacrylamide gel electrophoresis. Further we analyzed electrophysiologically the D2 dopamine receptor expressed in Xenopus Oocyte after injection of poly(A)RNA. We attempted to analyze the structure of the D2 dopamine receptor gene in schizophrenia. We succeeded in cloning the genomic DNA for D2 dopamine receptor and clarified the structure of this gene. This gene spans 15 kbp and consists of 7 exons interrupted by 6'introns. Spot-blot hybridization analysis of fractionated human chromosomal DNA with D2 receptor "enomic DNA revealed the localization of this gene in the chromosome I 1. We analyzed human genomic DNA by Southem blot analysis, but so far we could not find restriction fragment length polymorphism(RFLP)in schizophrenia. We are trying to detect the differences of the sequences of dopamine D2 receptor gene between normal and schizophrenia by single strand conformation polymorphism(SSCP).

多巴胺和多巴胺受体可能参与运动和情绪平衡。多巴胺D2受体对抗精神病药物具有高亲和力。TLiis受体还可能与帕金森病和精神分裂症的发病有关。采用光亲和标记、高效液相色谱和制备型十二烷基硫酸钠聚丙烯酰胺凝胶电泳纯化了牛脑D2多巴胺受体蛋白。进一步，我们对注射poly（A）RNA后非洲爪蟾卵母细胞表达的D2多巴胺受体进行了电生理分析。我们试图分析D2多巴胺受体基因的结构在精神分裂症。我们成功地克隆了D2多巴胺受体基因组DNA，并阐明了该基因的结构。该基因全长15kbp，由7个外显子和6 '内含子组成。将分离的人染色体DNA与D2受体基因组DNA进行斑点杂交分析，发现该基因位于染色体I1上。我们用Southem印迹分析了人类基因组DNA，但迄今为止，我们还没有发现精神分裂症的限制性片段长度多态性（RFLP）。本研究采用单链构象多态性（SSCP）技术，探讨多巴胺D2受体基因在正常人和精神分裂症患者中的差异。