EXPRESSION AND FUNCTION OF FMRP DURING DEVELOPMENT

我们的实验室最近从体外培养中获得了证据 突触神经体制备即脆性X基因产物，一种蛋白质 被称为FMRP，是从突触附近位置的mRNA翻译而来的 对谷氨酸能激活代谢性受体的反应。这 发现补充了脆性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可能在 在发育和/或突触活动过程中的作用 学习会导致突触的结构和功能成熟。 我们提出了一系列关于啮齿类动物大脑的基础研究，旨在 在体内进一步探讨：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，顺序 探讨FMRP病理效应的可能原因 大脑发育的缺陷，以及3)行为的影响 FMRP在已知表现为结构性脑区的表达经验 行为经验操作反应的可塑性，研究 单眼剥夺动物和暴露于苯系物的动物的视皮层 特技运动后动物丰富的环境和运动皮质 技能学习。脆性X综合征，可由一种突变引起 防止基因表达或影响结构的点突变 基因产物，是遗传性精神疾病最常见的形式之一 已知发育迟缓。此外，它通常与自闭症和 注意缺陷多动障碍。了解FMRP在以下方面的作用 突触成熟和脑功能很可能导致治疗 这些症状。

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.