EXPRESSION AND FUNCTION OF FMRP DURING DEVELOPMENT

FMRP 在发育过程中的表达和功能

• 批准号: 6530809
• 负责人: SCOTT A IRWIN
• 金额: $ 1.34万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-21 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6530809
• 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获得了证据 突触尿素的制剂，即脆弱的X基因产物，一种蛋白质 称为fMRP，从突触附近的位置的mRNA翻译 对代谢受体的谷氨酸能激活的反应。 这 查找对脆弱X基因（FMR-1）和 脆弱的X综合征，一种智力低下的形式与 没有正常的FMRP表达，所有这些都表明FMRP可能会播放 在开发过程中的突触活动和/或 学习导致突触的结构和功能成熟。 我们提出了一系列针对啮齿动物大脑的基础研究 进一步探索体内，1）表达的时空模式 FMRP在开发过程中，2）FMRP表达的可能相关性 与其他主要的发育过程（例如突触发生） 探索FMRP病理影响的可能原因 对大脑发育的缺陷和3）行为的影响 在已知表现出结构的大脑区域中FMRP表达的经验 响应行为经验操纵的可塑性，研究 暴露于单眼剥夺的动物中的视觉皮质 杂技马达后，动物的富集环境和运动皮层 技能学习。脆弱的X综合征，这可能是由突变引起的 防止基因表达或从影响结构的点突变 在基因产品中，是继承心理的最常见形式之一 已知迟钝。此外，它通常与自闭症和 注意缺陷多动障碍。了解FMRP在 突触的成熟和大脑功能很可能会引起治疗 这些综合征。