Akaba Yuichi, Shiohama Tadashi, Komaki Yuji, Seki Fumiko, Ortug Alpen, Sawada Daisuke, Uchida Wataru, Kamagata Koji, Shimoji Keigo, Aoki Shigeki, Takahashi Satoru, Suzuki Takeshi, Natsume Jun, Takahashi Emi, Tsujimura Keita
Group of Brain Function and Development, Nagoya University Neuroscience Institute of the Graduate School of Science, Nagoya, Japan.
Research Unit for Developmental Disorders, Institute for Advanced Research, Nagoya University, Nagoya, Japan.
Front Neurosci. 2022 May 10;16:885335. doi: 10.3389/fnins.2022.885335. eCollection 2022.
Rett syndrome (RTT) is a severe progressive neurodevelopmental disorder characterized by various neurological symptoms. Almost all RTT cases are caused by mutations in the X-linked methyl-CpG-binding protein 2 () gene, and several mouse models have been established to understand the disease. However, the neuroanatomical abnormalities in each brain region of RTT mouse models have not been fully understood. Here, we investigated the global and local neuroanatomy of the gene-deleted RTT model (-KO) mouse brain using T2-weighted 3D magnetic resonance imaging with different morphometry to clarify the brain structural abnormalities that are involved in the pathophysiology of RTT. We found a significant reduction in global and almost all local volumes in the brain of -KO mice. In addition, a detailed comparative analysis identified specific volume reductions in several brain regions in the -deficient brain. Our analysis also revealed that the -deficient brain shows changes in hemispheric asymmetry in several brain regions. These findings suggest that MeCP2 affects not only the whole-brain volume but also the region-specific brain structure. Our study provides a framework for neuroanatomical studies of a mouse model of RTT.
瑞特综合征（RTT）是一种严重的进行性神经发育障碍，其特征为多种神经症状。几乎所有的RTT病例都是由X连锁甲基化CpG结合蛋白2（MeCP2）基因突变引起的，并且已经建立了多种小鼠模型来研究该疾病。然而，RTT小鼠模型各个脑区的神经解剖学异常尚未完全明确。在此，我们使用具有不同形态测量方法的T2加权三维磁共振成像技术，研究了MeCP2基因敲除（MeCP2-KO）的RTT模型小鼠脑的整体和局部神经解剖结构，以阐明参与RTT病理生理学过程的脑结构异常。我们发现，MeCP2-KO小鼠脑的整体及几乎所有局部体积均显著减小。此外，详细的比较分析确定了MeCP2缺陷型脑的几个脑区存在特定的体积减小。我们的分析还表明，MeCP2缺陷型脑在几个脑区显示出半球不对称性的变化。这些发现表明，MeCP2不仅影响全脑体积，还影响特定区域的脑结构。我们的研究为RTT小鼠模型的神经解剖学研究提供了一个框架。
