SPINE MORPHOLOGY IN AN ANIMAL MODEL OF FRAGILE X SYNDROME

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 脆性X智力低下是一种遗传性疾病，是由于不能产生蛋白质FMRP而引起的。 FMRP表达的缺乏与人类死后组织和该疾病的小鼠模型中树突棘形态的改变有关。 此外，棘形状的稳定性已被证明是依赖于丝状形式的肌动蛋白，F-肌动蛋白。 对人类尸检组织和脆性X染色体智力低下综合征小鼠模型的高尔基体浸渍研究表明，树突棘具有不发达的外观-倾向于细长，曲折的棘形态。 我们已经初步假设，缺乏脆性X蛋白（FMRP）干扰突触和树突的成熟。 与NCMIR，我们将检查树突状节段使用高电压EM和NCMIR的最近开发的肌动蛋白染色方法，提供3-D图像的树突和他们的刺，以评估和提供更多的细节方面的成熟假说。

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 mental retardation, a genetically-linked disorder, results from the inability to produce the protein FMRP. The lack of FMRP expression has been associated with altered dendritic spine morphology in human post-mortem tissue and a mouse model of the disorder. Moreover, stability of spine shape has been shown to be dependent upon the filamentous form of actin, F-actin. Golgi-impregnation studies of human autopsy tissue and of a mouse model of fragile X mental retardation syndrome suggest that dendritic spines have an underdeveloped appearance--a tendency towards elongated, tortuous spine morphology. We have tentatively hypothesized that the absence of the fragile X protein (FMRP) interferes with synaptic and dendritic maturation. With the NCMIR this we will examine dendritic segments using high voltage EM and NCMIR's recently developed actin staining methodology to provide 3-D images of dendrites and their spines to evaluate and provide more details with respect to the maturation hypothesis.