CONTRIBUTION OF FXYD1 TO THE NEUROPATHOLOGY OF RETT SYNDROME

这个子项目是许多利用 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的目标是确定一个名为FXYD 1的基因在Rett综合征（RTT）的神经病理学中所起的作用。该综合征是一种与MECP 2基因中的杂合性新生突变相关的X连锁神经发育障碍。在缺乏MECP 2的情况下，FXYD 1基因在人类和Mecp 2缺失小鼠中均过表达。FXYD 1编码Na+，K+-ATP酶活性的跨膜调节剂。这些和其他观察结果表明，FXYD 1是MeCP 2靶基因，其去抑制可能直接导致RTT神经发病机制。所获得的结果表明，通过遗传手段降低FXYD 1表达，除了影响额叶皮层神经元的形态缺陷之外，还挽救了在没有MECP 2的情况下观察到的学习和记忆缺陷。

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. The goal of this project, now completed, was to define the role played by a gene termed FXYD1 in the neuropathology of Rett syndrome (RTT). This syndrome is an X-linked neurodevelopmental disorder linked to heterozygous de novo mutations in the MECP2 gene. In the absence of MECP2, the FXYD1 gene is overexpressed in both humans and Mecp2-null mice. FXYD1 encodes a trans-membrane modulator of Na+, K+-ATPase activity. These and other observations suggest that FXYD1 is a MeCP2 target gene whose de-repression may directly contribute to RTT neuropathogenesis. The results obtained indicate that decreasing FXYD1 expression by genetic means rescues learning and memory defects seen in the absence of MECP2, in addition to morphological deficiencies affecting neurons of the frontal cortex.