Regulation of Odorant Receptor Gene Expression in Olfactory Sensory Neurons

嗅觉感觉神经元中气味受体基因表达的调节

• 批准号: 7712615
• 负责人: Qizhi Gong
• 金额: $ 19.13万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7712615
• 关键词: Adrenergic Receptor; Afferent Neurons; Amino Acid Sequence; Axon; Cell Adhesion Molecules; Cell surface; Cells; Chemicals; Clinical; Discrimination; Environment; Foundations; Future; G-Protein-Coupled Receptors; Gene Expression; Genetic Transcription; Goals; Image; Immunoglobulin Domain; In Vitro; Individual; Intervention; Investigation; Label; Measures; Mediating; Monitor; Mus; Odorant Receptors; Peptide Sequence Determination; Play; Receptor Gene; Regulation; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Role; Specificity; System; Testing; Time; Transcriptional Regulation; Translating; axon guidance; design; genetic manipulation; immunocytochemistry; in vivo; insight; member; mouse genome; public health relevance; receptor expression; research study

DESCRIPTION (provided by applicant): Olfactory discrimination is achieved through chemical specificity of odorant receptors (OR) and their stereotypic olfactory connections. ORs are members of a large subfamily of G-protein coupled receptors (GPCR). There are about 1000 OR genes in the mouse genome. Each olfactory sensory neuron (OSN) chooses to express only one OR and converges its axon according to its OR identity to a stereotypic glomerulus. It is not clear how the OR selection is made and maintained within the OSN. OR proteins appear to play critical roles in OSN specificity in its OR expression and axon targeting. The goal of this study is to dissect the regulatory motif within the OR protein sequence in order to define the mechanism of OR- mediated transcription regulation. To carry out this study, we established an in vitro system which allows efficient genetic manipulation of OR expression within its intrinsic cellular environment, the OSN. Utilizing this in vitro system, in Aim 1, we will examine whether exogenous OR expression suppresses endogenous OR transcription in a sequence specific manner. In Aim 2, we will examine whether OR expression regulates adhesion molecule expression in OSNs. Through dissecting OR sequence and their regulatory function, we hope to gain insights into the mechanisms of OR expression choice and OSN axon guidance. Identification of the OR regulatory motif will lay foundations for future in vivo investigations and aid in the design of clinical interventions. PUBLIC HEALTH RELEVANCE: This study aims to understand the regulatory mechanism that controls the identity of olfactory sensory neurons in their odorant receptor choice and their expression of adhesion molecules for axon targeting.

描述（由申请人提供）：嗅觉辨别是通过气味受体（OR）的化学特异性及其刻板的嗅觉连接来实现的。 OR 是 G 蛋白偶联受体 (GPCR) 大亚家族的成员。小鼠基因组中约有1000个OR基因。每个嗅觉感觉神经元 (OSN) 选择仅表达一个 OR，并根据其 OR 身份将其轴突汇聚到刻板肾小球。目前尚不清楚 OR 选择是如何在 OSN 内进行和维护的。 OR 蛋白似乎在其 OR 表达和轴突靶向的 OSN 特异性中发挥着关键作用。本研究的目的是剖析 OR 蛋白序列内的调节基序，以确定 OR 介导的转录调节机制。为了进行这项研究，我们建立了一个体外系统，该系统允许在其内在细胞环境 OSN 内对 OR 表达进行有效的遗传操作。利用这个体外系统，在目标 1 中，我们将检查外源 OR 表达是否以序列特异性方式抑制内源 OR 转录。在目标 2 中，我们将检查 OR 表达是否调节 OSN 中粘附分子的表达。通过剖析OR序列及其调控功能，我们希望深入了解OR表达选择和OSN轴突引导的机制。 OR 调控基序的识别将为未来的体内研究奠定基础，并有助于临床干预措施的设计。公共健康相关性：本研究旨在了解控制嗅觉感觉神经元在气味受体选择中的身份以及用于轴突靶向的粘附分子表达的调节机制。