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Cited by 221Genetics and Neurodevelopmental DisordersGenomics and Rare DiseasesNeuroscience and Neuropharmacology Research

MECP2 disorders: from the clinic to mice and back

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Lombardi, Laura Marie, Baker, Steven Andrew, Zoghbi, Huda Yahya·2015·Journal of Clinical Investigation
DOI 10.1172/jci78167PMC PMC4563741
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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.

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  • Rett syndrome is a pervasive neurodevelopmental disorder caused in most cases by loss-of-function mutations in the X-linked gene MECP2.

    “This is now also the case with Rett syndrome, a pervasive neurodevelopmental disorder caused in most cases by loss-of-function mutations in the X-linked gene, methyl-CpG-binding protein 2 (MECP2) (Lombardi et al., 2015; Lyst and Bird, 2015).”

    From Suppression of brain cholesterol synthesis in male Mecp2-deficient mice is age dependent and not accompanied by a concurrent change in the rate of fatty acid synthesis (2017) · cites this paper as Lombardi et al., 2015

  • The consequences of MeCP2 dysfunction on neuronal networks have been extensively explored in mice lacking MeCP2 and those with a conditional hemizygous deletion, but the results vary considerably possibly due to differences in the age of the mice in the analysis and the specific characteristics of each cortical area.

    “The consequences of MeCP2 dysfunction on neuronal networks have been extensively explored in mice lacking MeCP2 and those with a conditional hemizygous deletion, but the results vary considerably possibly due to differences in the age of the mice in the analysis (juvenile, young adults and adults) and the specific characteristics of each cortical area 123,124 .”

    From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [124]

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Authors
Lombardi, L. M., Baker, S. A., & Zoghbi, H. Y.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Baylor College of Medicine (US)
Corresponding author
Zoghbi, Huda Yahya
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2015-08-03
Volume
125
Issue
8
Pages
2914-2923
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci78167
PMC
PMC4563741
OpenAlex
W2108328933
Cited by
221
References
0
Citations by year
2026: 10 · 2025: 15 · 2024: 17 · 2023: 6 · 2022: 14 · 2021: 26 · 2020: 23 · 2019: 16 · 2018: 26 · 2017: 37 · 2016: 29 · 2015: 1
FWCI
3.93
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • International Rett Syndrome Foundation
  • Rett Syndrome Research Trust
  • National Institute of Neurological Disorders and Stroke (NS057819, R01NS057819)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
MeCP2, Rett syndrome, MECP2 duplication syndrome, intellectual disability, autism spectrum disorder, developmental regression, mouse model, neuronal dysfunction, chromatin regulation
MeSH terms
Animals, Disease Models, Animal, Humans, Neurons, Rett Syndrome, Cell Death, Mental Retardation, X-Linked, X-Linked Intellectual Disability, Chromatin Assembly and Disassembly, Mice, Methyl-CpG-Binding Protein 2

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