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EXPRESSION AND FUNCTION OF FMRP DURING DEVELOPMENT

FMRP 在发育过程中的表达和功能

基本信息

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
项目类别：
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

项目摘要

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一个体外实验中获得了证据，突触神经体制备即脆性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，对代谢型受体的代谢能激活的反应。这这一发现补充了脆性X基因（FMR-1）和脆性X综合征，一种与正常FMRP表达的缺失，所有这些都表明FMRP可能发挥作用，在发育过程中突触活动的过程中的作用和/或学习导致突触的结构和功能成熟。我们提出了一系列啮齿动物大脑的基础研究，进一步探索在体内，1）表达的时空模式 FMRP在发育过程中的表达，2）FMRP表达的可能相关性与其他主要的发育过程，如突触发生，探讨FMRP病理效应的可能原因对大脑发育的影响，以及3）行为的影响在已知表现出结构性的脑区中FMRP表达的经验可塑性的行为经验的操纵，研究单眼剥夺动物和暴露于丰富的环境，和运动皮层的动物后，杂技运动技能学习脆性X染色体综合征，可能由突变引起，防止基因表达或点突变影响结构基因产物，是遗传性精神疾病最常见的形式之一。延迟已知此外，它通常与自闭症有关，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可能会产生治疗这些症状。