Function of FMRP in the Mouse Olfactory System

FMRP 在小鼠嗅觉系统中的功能

• 批准号: 6680556
• 负责人: JOHN R LARSON
• 金额: $ 23.3万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6680556
• 关键词: RNA binding protein; behavior test; depression; disease /disorder model; electrophysiology; fragile X syndromes; gene targeting; genetically modified animals; immunocytochemistry; laboratory mouse; learning; long term potentiation; memory disorders; mental retardation; neurobiology; olfactory lobe; olfactory stimulus; protein structure function; sensory discrimination; synapses; western blottings

DESCRIPTION (provided by applicant): Fragile X syndrome is the most common inherited cause of mental retardation. The disorder is caused by mutation in a gene, FMR1, that encodes the fragile X mental retardation protein (FMRP). How loss of FMRP produces mental retardation is not known. FMR1 knockout mice have been produced, providing a mouse model for fragile X syndrome. The experiments proposed in this application will use the mouse olfactory system to investigate the normal function of FMRP and the consequences of the protein's absence in knockout mice. FMRP is normally expressed in olfactory brain structures. The project has three specific aims. First, behavioral analyses will be conducted to determine how lack of FMRP results in impairment of memory formation for olfactory information. Second, electrophysiological methods will be used to determine how absence of FMRP alters synaptic function and synaptic plasticity in the primary olfactory cortex. Third, olfactory stimulation and learning paradigms will be used to determine how expression of FMRP is regulated by neuronal activity in the olfactory system. The results of these studies should provide new information regarding the function of FMRP in the normal brain and may identify behavioral or physiological functions that are reliably disrupted in mice lacking this important protein. Such new information would be vital for evaluating novel treatment strategies for a class of developmental disabilities.

描述（由申请人提供）：脆性 X 综合征是智力低下最常见的遗传原因。这种疾病是由 FMR1 基因突变引起的，该基因编码脆性 X 智力迟钝蛋白 (FMRP)。 FMRP 缺失如何导致智力低下尚不清楚。 FMR1 基因敲除小鼠已经生产出来，为脆性 X 综合征提供了小鼠模型。本申请中提出的实验将使用小鼠嗅觉系统来研究 FMRP 的正常功能以及该蛋白在基因敲除小鼠中缺失的后果。 FMRP 通常在嗅觉脑结构中表达。该项目有三个具体目标。首先，将进行行为分析以确定缺乏 FMRP 如何导致嗅觉信息记忆形成受损。其次，电生理学方法将用于确定 FMRP 的缺失如何改变初级嗅觉皮层的突触功能和突触可塑性。第三，嗅觉刺激和学习范式将用于确定嗅觉系统中神经元活动如何调节 FMRP 的表达。这些研究的结果应该提供有关正常大脑中 FMRP 功能的新信息，并可能确定缺乏这种重要蛋白质的小鼠的行为或生理功能被可靠地破坏。这些新信息对于评估一类发育障碍的新治疗策略至关重要。