Fragile X Syndrome: Banbury Conferences

描述(由申请人提供)：本提案请求支持关于脆性X综合征(FXS)的班伯里会议延续5年。包括第一次会议在内，已经在纽约长岛冷泉港实验室的班伯里会议中心举行了六次这样的会议。我们提出了一系列关于脆性X综合征(FXS)基础和临床研究的五个年度跨学科会议。这些会议旨在将范围广泛的科学家聚集在一起，既有从事FXS工作的科学家，也有其他相关领域的科学家。另一个目标是将年轻的科学家，包括女性和少数民族，引入该地区。脆性X综合征是导致智力低下的最常见的遗传性原因。它的产生是由于FMR-1基因5‘端未翻译启动子区域三核苷酸重复序列的不稳定区域的扩张，导致胞嘧啶残基的高甲基化，通常导致基因沉默。许多针对该综合征的小鼠FMR-1基因敲除模型已经或即将推出。脆性X智力低下蛋白(FMRP)的功能被认为是一组具有不同细胞功能的mRNAs的运输和翻译调节。FMRP似乎是在突触上翻译的，以响应代谢性谷氨酸受体的激活。在人类和基因敲除小鼠模型中，这种疾病的相对微妙的表型效应可以在几个大脑区域的粗大尺寸中看到，在突触的精细结构中也可以看到。正如班伯里会议所表明的那样(摘要见SEC.C)，我们对这种疾病的认识进展非常迅速。没有其他会议专门讨论FXS的基础和临床研究，与会者一致认为班伯里会议非常有价值。

DESCRIPTION (provided by applicant): This proposal requests support for a 5 year continuation of the Banbury Conferences on Fragile X syndrome (FXS). Including an initial conference, six such meetings have been held at Banbury Conference Center at Cold Spring Harbor Laboratory on Long Island NY. We propose a series of five annual interdisciplinary conferences on basic and clinical research relevant to fragile X syndrome (FXS). The conferences are intended to bring together a broad range of scientists, both those working on FXS and others in allied, relevant fields. Another goal is to introduce young scientists, including females and minorities, to the area. Fragile X syndrome is the most common inherited cause of mental retardation. It arises due to expansion of an unstable region of trinucleotide repeats in the 5' untranslated promoter region of the FMR-1 gene, causing hypermethylation of cytosine residues and, generally, silencing of the gene. A number of mouse FMR-1 knockout models for the syndrome have or are about to become available. The function of the fragile X mental retardation protein (FMRP) is believed to be the transport and translational regulation of a subset of mRNAs with a diverse set of cellular functions. FMRP appears to be translated at synapses in response to activation of metabotropic glutamate receptors. Relatively subtle phenotypic effects of the disorder are seen in the gross size of several brain regions and in the fine structure of synapses in humans and in the knockout mouse model. As the Banbury Conferences have made clear (summarized in Sec. C), advances in our knowledge of this disorder are occurring very rapidly. There is no other meeting devoted exclusively to basic and clinical research on FXS, and the participants consistently report the Banbury Conference to be extremely valuable.