SCREEN FOR FRAGILE X MUTATIONS IN PRIMATES

筛选灵长类动物中的脆性 X 突变

• 批准号: 7958999
• 负责人: PAUL J HAGERMAN
• 金额: $ 3.56万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958999
• 关键词: 5' Untranslated Regions; Animal Model; Anxiety; Behavior; Blood specimen; CGG repeat; CGG repeat expansion; California; Cells; Computer Retrieval of Information on Scientific Projects Database; FMR1 Gene; FXTAS; Fragile X Mental Retardation Protein; Fragile X Premutation; Fragile X Syndrome; Funding; Generations; Grant; Human; Individual; Inherited; Institution; Lead; Learning Disabilities; Macaca; Macaca mulatta; Mental Retardation; Messenger RNA; Molecular; Mutation; Neurodegenerative Disorders; Primates; Proteins; Research; Research Personnel; Resources; Social Phobia; Source; Toxic effect; Translational Regulation; United States National Institutes of Health; Woman; genetic pedigree; human subject; trait

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Fragile X syndrome, the most common inherited form of mental retardation, arises in individuals with more than 200 CGG repeats in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene. In humans, approximately 1 in 260 women, is a carrier of the expanded (55 to 200) CGG repeat. We have identified a rhesus macaque pedigree with 5 subject carriers of an expanded CGG region in the premutation range. Human subject carriers of fragile X premutations express higher levels of FMR1-mRNA, between 2 to 10 fold in blood samples. The increased FMR1 expression can lead to cell toxicity over the years and be the cause of Fragile X associated tremor ataxia syndrome (FXTAS) a newly described neurodegenerative disease. It has also been observed that premutation carriers often express lower levels of fragile X protein (FMRP) that presumably causes social phobia, autistic-like behavior, anxiety, OCD, psychotic traits and learning disability. This pedigree represents the first animal model that spontaneously carries an expanded repeat. FMR1 mRNA and protein levels have not yet been analyzed in macaque carriers of expansions of CGG repeats in FMR1. By examining FMR1 gene and related proteins in this pedigree we expect to make progress in the understanding of the molecular mechanisms leading to the expansion of the CGG repeats in succeeding generations, as well as identifying factors involved in transcriptional-translational regulation.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 脆弱的X综合征是最常见的智力低下遗传形式，是在脆弱的X智力低下1（FMR1）基因的5'未翻译区域中重复200多个CGG重复的个体中产生的。在人类中，大约260名女性中约有1个是扩张（55至200）CGG重复的载体。我们已经确定了恒河猴猕猴的血统，并在预告范围内有5个扩展的CGG区域的主题载体。脆弱X预言的人类受试者载体表达了更高水平的FMR1-MRNA，在血液样本中2至10倍之间。多年来，FMR1表达增加会导致细胞毒性，并成为脆弱的X相关震颤性共济失调综合征（FXTA）的原因。还观察到，预先享有的载体通常表达较低的脆弱X蛋白（FMRP），可能会导致社交恐惧症，自闭症行为，焦虑，强迫症，精神病性质和学习障碍。该谱系代表了自发重复扩展的第一个动物模型。 FMR1 mRNA和蛋白质水平尚未在FMR1中CGG重复膨胀的猕猴载体中进行分析。通过检查该谱系中的FMR1基因和相关蛋白质，我们期望在了解后代的CGG重复序列扩展的分子机制方面取得进展，并识别转录转录 - 转录调节涉及的因素。