CONSTITUTIVELY ACTIVE RECEPTORS IN PSYCHIATRIC DISEASE

精神疾病中的组成型活性受体

• 批准号: 6073682
• 负责人: DAVID M WEINER
• 金额: $ 11.95万
• 依托单位: ACADIA PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6073682
• 关键词: clinical research; gene mutation; genetic screening; human subject; mental disorders; molecular cloning; molecular genetics; nervous system disorder; neurogenetics; neuropsychology; neurotransmitter receptor; nucleic acid sequence; phenotype; polymerase chain reaction; protein structure function; psychiatry; receptor expression

The search for the genetic basis of neuropsychiatric disease is a major focus of current research in biologic psychiatry. Alterations in monoaminergic neurotransmission are thought to have a pathophysiologic role in many neuropsychiatric disorders. We intend to approach the study of the genetics of neuropsychiatric disease using a candidate gene approach, focusing on the potential role of constitutively activated monoaminergic neurotransmitter receptors. We intend to apply a novel phenotypic assay of receptor function, R-SAT (Receptor Selection and Amplification Technology), to screen patient populations for constitutively active monoaminergic receptors. R-SAT screening involves the high throughput PCR amplification and subcloning of receptor sequences from a patient's genomic DNA, coupled to their transient expression in mammalian cells for phenotypic analysis. Constitutively active receptors will be identified and the causative mutations will be determined by DNA sequencing. This data will enable us to conduct traditional population based genetic studies to assess, the prevalence and role of constitutively active receptors in neuropsychiatric disease. PROPOSED COMMERCIAL APPLICATIONS: The identification of a genetic cause of a major mental illness would create two significant commercial opportunities. 1) The creation of a diagnostic test for the disease in question, and 2) the knowledge necessary to design a specific, potentially curable, therapeutic agent for the disease in question.

寻找神经精神病学疾病的遗传基础是当前生物精神病学研究的主要焦点。单胺能神经传递的改变被认为在许多神经精神障碍中具有病理生理学作用。我们打算使用候选基因方法来研究神经精神疾病的遗传学，重点是结构性激活的单胺能神经递质受体的潜在作用。我们打算应用一种新的受体功能表型分析R-SAT(受体选择和放大技术)来筛选患者群体中具有结构性活性的单胺类受体。R-SAT筛选包括从患者基因组DNA中高通量扩增和亚克隆受体序列，以及它们在哺乳动物细胞中的瞬时表达，以进行表型分析。将通过DNA测序来确定构成活性的受体和致病突变。这些数据将使我们能够进行传统的基于人群的遗传学研究，以评估神经精神疾病中结构性活性受体的患病率和作用。拟议的商业应用：确定一种主要精神疾病的遗传原因将创造两个重要的商业机会。1)创建对所述疾病的诊断测试，以及2)为所述疾病设计特定的、潜在可治愈的治疗剂所需的知识。