Analysis of human D2 dopamine receptor gene in schizophrenia

多巴胺和多巴胺受体可能参与运动和情绪平衡。D2多巴胺受体与抗精神病药物具有较高的亲和力。Tliis受体也可能与帕金森氏病和精神分裂症的发病有关。我们用光亲和标记法、高效液相层析和制备十二烷基硫酸钠-聚丙烯酰胺凝胶电泳法纯化了牛脑D2多巴胺受体蛋白。进一步，我们对注射聚(A)RNA后非洲爪哇卵母细胞中表达的D2多巴胺受体进行了电生理学分析。我们试图分析精神分裂症患者D2多巴胺受体基因的结构。我们成功地克隆了D2多巴胺受体的基因组DNA，并阐明了该基因的结构。该基因全长15kbp，由7个外显子组成，中间有6‘个内含子。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，发现该基因定位于第1号染色体。我们用Souhim杂交分析了人类基因组DNA，但迄今在精神分裂症中没有发现限制性片段长度多态性(RFLP)，我们试图用单链构象多态性(SSCP)检测正常人和精神分裂症患者多巴胺D2受体基因序列的差异。

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).