title: MECP2 disorders: from the clinic to mice and back.
abstract: Two severe, progressive neurological disorders characterized by intellectual disability, autism, and developmental regression, Rett syndrome and MECP2 duplication syndrome, result from loss and gain of function, respectively, of the same critical gene, methyl-CpG-binding protein 2 (MECP2). Neurons acutely require the appropriate dose of MECP2 to function properly but do not die in its absence or overexpression. Instead, neuronal dysfunction can be reversed in a Rett syndrome mouse model if MeCP2 function is restored. Thus, MECP2 disorders provide a unique window into the delicate balance of neuronal health, the power of mouse models, and the importance of chromatin regulation in mature neurons. In this Review, we will discuss the clinical profiles of MECP2 disorders, the knowledge acquired from mouse models of the syndromes, and how that knowledge is informing current and future clinical studies.
authors.forename: Laura Marie
authors.initials: LM
authors.lastname: Lombardi
authors.forename: Steven Andrew
authors.initials: SA
authors.lastname: Baker
authors.forename: Huda Yahya
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C497392:MECP2 protein, human; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2