Genetic Metabolic Disorders Research Unit, Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
Molecular Neurobiology Research Group, Kids Research, Sydney Children's Hospitals Network, Westmead, Australia.
Hum Mutat. 2019 Dec;40(12):2184-2196. doi: 10.1002/humu.23887. Epub 2019 Aug 23.
The discovery that Rett syndrome is caused by mutations in the MECP2 gene has provided a major breakthrough in our understanding of the disorder. However, despite this, there is still limited understanding of the underlying pathophysiology of the disorder hampering the development of curative treatments. Over the years, a number of animal models have been developed contributing to our knowledge of the role of MECP2 in development and improving our understanding of how subtle expression levels affect brain morphology and function. Transcriptomic and proteomic studies of animal models are useful in identifying perturbations in functional pathways and providing avenues for novel areas of research into disease. This review focuses on published transcriptomic and proteomic studies of mouse models of Rett syndrome with the aim of providing a summary of all the studies, the reported dysregulated genes and functional pathways that are found to be perturbed. The 36 articles identified highlighted a number of dysfunctional pathways as well as perturbed biological networks and cellular functions including synaptic dysfunction and neuronal transmission, inflammation, and mitochondrial dysfunction. These data reveal biological insights that contribute to the disease process which may be targeted to investigate curative treatments.
Rett 综合征是由 MECP2 基因突变引起的这一发现,为我们理解这种疾病提供了重大突破。然而,尽管如此,我们对这种疾病的潜在病理生理学仍知之甚少,这阻碍了治愈方法的发展。多年来,已经开发了许多动物模型,这些模型有助于我们了解 MECP2 在发育中的作用,并加深我们对微妙的表达水平如何影响大脑形态和功能的理解。对动物模型的转录组和蛋白质组学研究有助于确定功能途径的干扰,并为疾病的新研究领域提供途径。这篇综述重点介绍了已发表的 Rett 综合征小鼠模型的转录组学和蛋白质组学研究,旨在总结所有研究报告的失调基因和功能途径。确定的 36 篇文章强调了许多功能失调的途径以及失调的生物网络和细胞功能,包括突触功能障碍和神经元传递、炎症和线粒体功能障碍。这些数据揭示了可能成为治疗目标的疾病过程中的生物学见解。