CONTRIBUTION OF FXYD1 TO THE NEUROPATHOLOGY OF RETT 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。 这项现已完成的项目的目标是确定一种名为FXYD1的基因在Rett综合征(RTT)的神经病理学中所起的作用。这种综合征是一种X连锁的神经发育障碍，与MECP2基因的杂合从头突变有关。在缺乏MECP2的情况下，FXYD1基因在人类和MeCP2缺失的小鼠中都过度表达。FXYD1编码Na+，K+-ATPase活性的跨膜调节剂。这些和其他观察结果表明，FXYD1是一个MeCP2靶基因，其抑制可能直接参与RTT的神经发病。结果表明，通过遗传手段降低FXYD1的表达可以挽救在缺少MECP2的情况下出现的学习和记忆缺陷，以及影响额叶皮质神经元的形态缺陷。

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.