Molecular Mechanisms of Specific Anosmia

特异性嗅觉丧失的分子机制

• 批准号: 7249411
• 负责人: HANYI ZHUANG
• 金额: $ 1.58万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7249411
• 关键词: Anosmia; Biological Assay; Carrier Proteins; Cell surface; Cells; Chimera organism; Code; Genetic Polymorphism; Genotype; Human; Investigation; Ligands; Luciferases; Messenger RNA; Molecular; Mouse Strains; Mus; Odorant Receptors; Odors; Perception; Phenotype; Polymorphism Analysis; Population; Screening procedure; Series; Single Nucleotide Polymorphism; Structure; System; Testing; Ubiquitin; in vivo; mouse model; protein expression; receptor; research study; yeast two hybrid system

DESCRIPTION (provided by applicant): The project outlined in this application will focus on the molecular mechanism underlying mammalian odor perception through the investigations of specific anosmia and sensitization of androstenone and other ligands. Androstenone odorant receptor(s) will be identified using a screening system matching receptors to their cognate ligands. Such system will be strengthened by a structure-function analysis of the receptor- transporting proteins (RTPs). Deletion and chimeric series of RTPs will be assessed in cell-surface immunostaining and luciferase assay to identify key regions. Domains of interaction between RTPs and odorant receptors will be investigated using the split-ubiquitin yeast two-hybrid system. The polymorphisms in candidate androstenone odorant receptor(s) will be evaluated for correlation with the anosmic phenotype by genotyping a psychophysically-analyzed population. Mouse models of androstenone-anosmic and osmic strains will be used for similar SNP genotype analysis, as well as mRNA and protein expression analyses. In vivo sensitization and experiments in heterologous cell will shed lights how ligand exposure facilitates androstenone sensitization.

描述(由申请人提供)：本申请中概述的项目将通过研究特定的雄酮和其他配体的嗅觉丧失和敏化作用，重点研究哺乳动物气味感知的分子机制。雄激素气味受体(S)将使用将受体与其同源配体匹配的筛选系统进行鉴定。这种系统将通过对受体运输蛋白(RTP)的结构-功能分析来加强。RTP的缺失和嵌合序列将在细胞表面免疫染色和荧光素酶分析中进行评估，以确定关键区域。将使用裂解泛素酵母双杂交系统研究RTP和气味受体之间的相互作用区域。候选雄酮气味受体(S)的多态性将通过对心理生理分析的人群进行基因分型来评估与无嗅觉表型的相关性。雄酮缺乏症和渗透性品系的小鼠模型将用于类似的SNP基因分析，以及mRNA和蛋白质表达分析。体内敏化和异种细胞实验将揭示配体暴露如何促进雄激素敏化。