ABSTRACT

Methyl-CpG-binding protein (MeCP2) is highly expressed in neurons. It plays an important role in the development of synapses and the formation of circuits in the central nervous system (CNS). Mutations in MECP2 cause neurodevelopmental disorders and mental retardation in humans. Therefore, it has become important to determine the distribution and function of MeCP2 in vivo. The retina consists of three nuclear cell layers and two layers of synapses; neurons in each layer are connected to form fine circuits necessary for visual signal transduction. Using immunohistochemical analysis, we found that MeCP2 was expressed in all nuclear cell layers, with differences in the levels of MeCP2 expression observed among the layers. To understand the structural defects in the retina due to the loss of MeCP2, we sought to elucidate the organization of the retinal structure in the Mecp2 knockout (KO) mouse. Overall, we found a normal retinal structure in Mecp2 KO mice. However, because Mecp2 mutations have a highly variable effect on neuronal architecture, we analyzed morphological changes in a subset of retinal ganglion cells of Mecp2 KO mice. In Thy1-GFP mice crossed with Mecp2 mutant mice, Sholl intersections analyses showed a subtle increase in number of intersections due to increased branching proximal to the soma in Mecp2 KO mice. Our results demonstrate that the expression of MeCP2 and the effects of Mecp2 mutations are highly specific to tissue and cell types.

摘要

甲基-CpG结合蛋白（MeCP2）在神经元中高度表达。它在突触的发展和中枢神经系统（CNS）的回路形成中起重要作用。MECP2中的突变会导致人类神经发育障碍和智力低下。因此，确定MeCP2在体内的分布和功能已经变得很重要。。视网膜由三层核细胞层和两层突触层组成。每层中的神经元被连接以形成视觉信号转导所必需的精细电路。使用免疫组化分析，我们发现MeCP2在所有核细胞层中表达，并且在各层之间观察到MeCP2表达水平的差异。为了了解由于MeCP2缺失导致的视网膜结构缺陷，我们试图阐明Mecp2基因敲除（KO）小鼠的视网膜结构组织。总体而言，我们在Mecp2 KO小鼠中发现了正常的视网膜结构。但是，由于Mecp2突变对神经元结构的影响很大，因此我们分析了视网膜神经节细胞亚群中的形态学变化。Mecp2 KO小鼠。在与Mecp2突变小鼠杂交的Thy1-GFP小鼠中，Sholl交点分析显示，由于Mecp2 KO小鼠中靠近体的分支增加，交点数微妙增加。我们的结果表明，MeCP2的表达和Mecp2突变的影响对组织和细胞类型具有高度特异性。