Rett Syndrome (RTT) is a genetic disorder that is caused by mutations in the x-linked gene coding for methyl-CpG-biding-protein 2 (MECP2) and that mainly affects females. Male and female transgenic mouse models of RTT have been studied extensively, and we have learned a great deal regarding RTT neuropathology and how MeCP2 deficiency may be influencing brain function and maturation. In this manuscript we review what is known concerning structural and coinciding functional and behavioral deficits in RTT and in mouse models of MeCP2 deficiency. We also introduce our own corroborating data regarding behavioral phenotype and morphological alterations in volume of the cortex and striatum and the density of neurons, aberrations in experience-dependent plasticity within the barrel cortex and the impact of MeCP2 loss on glial structure. We conclude that regional structural changes in genetic models of RTT show great similarity to the alterations in brain structure of patients with RTT. These region-specific modifications often coincide with phenotype onset and contribute to larger issues of circuit connectivity, progression, and severity. Although the alterations seen in mouse models of RTT appear to be primarily due to cell-autonomous effects, there are also non-cell autonomous mechanisms including those caused by MeCP2-deficient glia that negatively impact healthy neuronal function. Collectively, this body of work has provided a solid foundation on which to continue to build our understanding of the role of MeCP2 on neuronal and glial structure and function, its greater impact on neural development, and potential new therapeutic avenues.

中文翻译：

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Rett综合征小鼠模型中神经发育和行为的变化轨迹。

Rett综合征（RTT）是一种遗传疾病，由编码甲基CpG抑制蛋白2（MECP2）的x连锁基因突变引起，主要影响女性。已经对RTT的雄性和雌性转基因小鼠模型进行了广泛的研究，并且我们已经了解了大量有关RTT神经病理学以及MeCP2缺乏可能如何影响脑功能和成熟的知识。在本手稿中，我们回顾了有关RTT和MeCP2缺乏症小鼠模型中结构性和协调性功能与行为缺陷的已知知识。我们还介绍了有关行为表型和皮质和纹状体体积以及神经元密度的形态变化，神经元密度，桶皮质内经验依赖的可塑性畸变以及MeCP2丢失对神经胶质结构的影响等方面的确证数据。我们得出结论，RTT遗传模型中的区域结构变化与RTT患者脑结构的变化非常相似。这些特定于区域的修饰通常与表型发作相吻合，并导致更大的电路连通性，进展和严重性问题。尽管在RTT小鼠模型中看到的变化似乎主要归因于细胞自主效应，但也存在非细胞自主机制，包括由MeCP2缺失胶质细胞引起的那些对健康神经元功能产生负面影响的机制。总的来说，这项工作为我们继续了解MeCP2在神经元和神经胶质结构和功能中的作用，其对神经发育的更大影响以及潜在的新治疗途径提供了坚实的基础。