Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation
Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation
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DOI：
10.1093/hmg/11.2.115
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发表时间：
2002-01-15
影响因子：
3.5
通讯作者：
Zoghbi, HY
中科院分区：
文献类型：
--
作者：
Shahbazian, MD;Antalffy, B;Zoghbi, HY
Rett 综合征 (RTT) 是一种由甲基 CpG 结合蛋白 2 (MECP2) 基因突变引起的神经发育障碍。之前的数据表明MECP2 RNA存在于所有测试的小鼠和人体组织中，但表达的时间和区域分布尚未被探索。我们研究了小鼠和人类发育过程中 MeCP2 蛋白的空间和时间分布。我们发现，在成年小鼠中，MeCP2 在脑、肺和脾中含量较高，在心脏和肾脏中含量较低，在肝脏、胃和小肠中几乎检测不到。蛋白质水平和RNA水平之间没有明显的相关性，表明翻译可能受到组织特异性因素的转录后调节。小鼠和人类中 MeCP2 表达的时间与中枢神经系统的成熟相关，个体发育较旧的结构（如脊髓和脑干）先于较新的结构（如海马和大脑皮层）变得阳性。在皮质中，MeCP2首先出现在Cajal-Retzius细胞中，然后出现在更深层、更成熟的皮质层的神经元中，最后出现在更浅层的神经元中。 MeCP2 蛋白最终存在于大多数神经元中，但在神经胶质细胞中不存在。我们的数据表明，只有当神经元达到一定程度的成熟时，MeCP2 才可能变得丰富，这可以解释 RTT 表型的某些方面。
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Previous data have shown that MECP2 RNA is present in all mouse and human tissues tested, but the timing of expression and regional distribution have not been explored. We investigated the spatial and temporal distribution of the MeCP2 protein during mouse and human development. We found that in the adult mouse, MeCP2 is high in the brain, lung and spleen, lower in heart and kidney, and barely detectable in liver, stomach and small intestine. There was no obvious correlation between protein levels and RNA levels, suggesting that translation may be post-transcriptionally regulated by tissue-specific factors. The timing of MeCP2 expression in mouse and human correlated with the maturation of the central nervous system, with the ontogenetically older structures such as the spinal cord and brainstem becoming positive before newer structures such as the hippocampus and cerebral cortex. In the cortex, MeCP2 first appeared in the Cajal-Retzius cells, then in the neurons of the deeper, more mature cortical layers, and finally in the neurons of the more superficial layers. The MeCP2 protein was eventually present in a majority of neurons but was absent from glial cells. Our data suggest that MeCP2 may become abundant only once a neuron has reached a certain degree of maturity, and that this may explain some aspects of the RTT phenotype.