EXPRESSION AND FUNCTION OF FMRP DURING DEVELOPMENT

FMRP 在发育过程中的表达和功能

• 批准号: 6363624
• 负责人: SCOTT A IRWIN
• 金额: $ 2.86万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-21 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6363624
• 关键词: developmental genetics; developmental neurobiology; fragile X syndromes; gene expression; health science research support; immunocytochemistry; laboratory rat; motor cortex; nerve /myelin protein; neurogenetics; point mutation; psychomotor function; synaptogenesis; synaptosomes; university student; visual cortex; western blottings

Our laboratory has recently obtained evidence from an in vitro synaptoneurosome preparation that the fragile X gene product, a protein termed FMRP, is translated from mRNA at locations near synapses in response to glutamatergic activation of metabotropic receptors. This finding complements other work on the fragile X gene (FMR-1) and the fragile X syndrome, a form of mental retardation correlated with the absence of normal FMRP expression, all of which suggest that FMRP may play a role in the process whereby synaptic activity during development and/or learning results in a structural and functional maturation of the synapse. We propose a series of basic studies of the rodent brain designed to further explore in vivo, 1) the spatio-temporal pattern of the expression of FMRP during development, 2) the possible correlation of FMRP expression with other major developmental processes, such as synaptogenesis, in order to explore possible reasons for the pathological effects of FMRP deficiencies on brain development, and 3) the effects of behavioral experience on FMRP expression in brain regions known to exhibit structural plasticity in response to behavioral experience manipulations, studying visual cortex in monocularly deprived animals and animals exposed to an enriched environment, and motor cortex in animals after acrobatic motor skill learning. Fragile X syndrome, which can arise from a mutation that prevents gene expression or from point mutations affecting the structure of the gene product, is one of the most common forms of inherited mental retardation known. Furthermore, it is commonly associated with autism and attention deficit hyperactivity disorder. Knowledge of the role of FMRP in synapse maturation and brain function may well give rise to treatments for these syndromes.

我们的实验室最近从体外实验中获得了证据 突触神经体制剂，脆弱的 X 基因产物，一种蛋白质 称为 FMRP，是从突触附近位置的 mRNA 翻译而来 对代谢型受体的谷氨酸激活的反应。 这 这一发现补充了有关脆弱 X 基因 (FMR-1) 和 脆性 X 综合征，一种与 缺乏正常的 FMRP 表达，所有这些都表明 FMRP 可能发挥作用 突触活动在发育和/或过程中的作用 学习导致突触结构和功能的成熟。 我们提出了一系列啮齿动物大脑的基础研究，旨在 进一步探索体内，1）表达的时空模式 FMRP在开发过程中的变化，2）FMRP表达的可能相关性 与其他主要发育过程（例如突触发生）一起进行 探讨FMRP病理效应的可能原因 对大脑发育的缺陷，以及3）行为的影响 已知表现出结构性的大脑区域 FMRP 表达的经验 对行为经验操纵的反应的可塑性，研究 单眼剥夺动物和暴露于光环境的动物的视觉皮层 杂技运动后丰富的环境和动物的运动皮层 技能学习。脆性 X 综合征，可能由以下突变引起： 防止基因表达或影响结构的点突变 基因产物，是遗传性心理最常见的形式之一 已知的延迟。此外，它通常与自闭症和 注意力缺陷多动障碍。了解 FMRP 在以下方面的作用： 突触成熟和大脑功能很可能会产生治疗方法 这些综合症。