SPINE MORPHOLOGY IN AN ANIMAL MODEL OF FRAGILE X SYNDROME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 脆性X智力低下是一种与基因有关的疾病，它是由于无法产生FMRP蛋白造成的。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，脊柱形状的稳定性已被证明依赖于肌动蛋白的丝状形式，即F-肌动蛋白。对人类尸检组织和脆性X智力低下综合征小鼠模型的高尔基浸渍研究表明，树突棘的外观不发达--有延长、曲折的脊柱形态的趋势。我们已经初步假设，脆性X蛋白(FMRP)的缺失会干扰突触和树突的成熟。有了NCMIR，我们将使用高压EM和NCMIR最近开发的肌动蛋白染色方法来检查树突节段，以提供树突及其棘突的3D图像，以评估和提供关于成熟假说的更多细节。

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.