Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), a progressive X-linked neurological disorder characterized by loss of developmental milestones, intellectual disability and breathing abnormality. Despite being a monogenic disorder, the pathogenic mechanisms by which mutations in MeCP2 impair neuronal function and underlie the RTT symptoms have been challenging to elucidate. The seemingly simple genetic root and the availability of genetic data from RTT patients have led to the generation and characterization of a series of mouse models recapitulating RTT-associated genetic mutations. This review focuses on the studies of RTT mouse models and describe newly obtained pathogenic insights from these studies. We also highlight the potential of studying pathophysiology using genetics-based modeling approaches in rodents and suggest a future direction to tackle the pathophysiology of intellectual disability with known or complex genetic causes.

中文翻译：

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利用雷特综合征的遗传基础来确定病理生理学。


甲基 CpG 结合蛋白 2 (MECP2) 基因突变会导致 Rett 综合征 (RTT)，这是一种进行性 X 连锁神经系统疾病，其特征是发育里程碑丧失、智力障碍和呼吸异常。尽管是一种单基因疾病，但 MeCP2 突变损害神经元功能并导致 RTT 症状的致病机制一直难以阐明。看似简单的遗传根源和 RTT 患者遗传数据的可用性导致了一系列重现 RTT 相关基因突变的小鼠模型的生成和表征。本综述重点关注 RTT 小鼠模型的研究，并描述从这些研究中新获得的致病性见解。我们还强调了在啮齿动物中使用基于遗传学的建模方法研究病理生理学的潜力，并提出了解决已知或复杂遗传原因的智力障碍病理生理学的未来方向。