Molecular Mechanisms of Specific Anosmia

特异性嗅觉丧失的分子机制

• 批准号: 7155985
• 负责人: HANYI ZHUANG
• 金额: $ 4.76万
• 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 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155985
• 关键词: anosmia; clinical research; genotype; ligands; receptor

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雄烯酮和其他配体的特异性嗅觉丧失和致敏作用，关注哺乳动物气味感知的分子机制。将使用将受体与其同源配体匹配的筛选系统来鉴定雄甾烯酮气味受体。通过对受体转运蛋白（RTPs）的结构-功能分析，将进一步加强这一系统。将在细胞表面免疫染色和荧光素酶测定中评估RTP的缺失和嵌合系列，以鉴定关键区域。RTPs和气味受体之间的相互作用域将使用分裂泛素酵母双杂交系统进行研究。通过对精神病理学分析的人群进行基因分型，评价候选雄甾烯酮气味受体的多态性与嗅觉缺失表型的相关性。雄甾烯酮-嗅觉缺失和嗅觉缺失品系的小鼠模型将用于类似的SNP基因型分析，以及mRNA和蛋白质表达分析。体内致敏和异源细胞实验将揭示配体暴露如何促进雄甾烯酮致敏。