Adult Neural Function Requires MeCP2
Open accessAbstract
Rett syndrome (RTT) is a postnatal neurological disorder caused by mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2 (MeCP2). The onset of RTT symptoms during early life together with findings suggesting neurodevelopmental abnormalities in RTT and mouse models of RTT raised the question of whether maintaining MeCP2 function exclusively during early life might protect against disease. We show by using an inducible model of RTT that deletion of Mecp2 in adult mice recapitulates the germline knock-out phenotype, underscoring the ongoing role of MeCP2 in adult neurological function. Moreover, unlike the effects of other epigenetic instructions programmed during early life, the effects of early MeCP2 function are lost soon after its deletion. These findings suggest that therapies for RTT must be maintained throughout life.
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The most likely explanation for this apparent discrepancy is that the proteins involved in these disorders also play important functions in the mature brain.
“The most likely explanation for this apparent discrepancy is that the proteins involved in these disorders also play important functions in the mature brain 133,134 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [134]
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- Authors
- McGraw, C. M., Samaco, R. C., & Zoghbi, H. Y.
- Affiliations
- Baylor College of Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Zoghbi, Huda Y.
- Venue
- Science
- Published
- 2011-07-08
- Volume
- 333
- Issue
- 6039
- Pages
- 186-186
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3150190
- OpenAlex
- W2005729136
- Cited by
- 255
- References
- 1
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 10 · 2023: 5 · 2022: 14 · 2021: 14 · 2020: 16 · 2019: 14 · 2018: 12 · 2017: 18 · 2016: 23 · 2015: 22 · 2014: 22 · 2013: 29 · 2012: 36
- FWCI
- 18.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (F31NS073317, NS057819, T32NS043124, R01NS057819)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 024064, P30HD024064)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Rett syndrome, MeCP2, epigenetic regulation, brain development, long-term treatment
- MeSH terms
- Aging, Animals, Disease Models, Animal, Gene Expression Regulation, Learning, Male, Memory, Nervous System Physiological Phenomena, Rett Syndrome, Mice, Knockout, Mice, Methyl-CpG-Binding Protein 2
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