Morphological and functional reversal of phenotypes in a mouse model of Rett syndrome
Open accessAbstract
Rett syndrome is a neurological disorder caused by mutation of the X-linked MECP2 gene. Mice lacking functional Mecp2 display a spectrum of Rett syndrome-like signs, including disturbances in motor function and abnormal patterns of breathing, accompanied by structural defects in central motor areas and the brainstem. Although routinely classified as a neurodevelopmental disorder, many aspects of the mouse phenotype can be effectively reversed by activation of a quiescent Mecp2 gene in adults. This suggests that absence of Mecp2 during brain development does not irreversibly compromise brain function. It is conceivable, however, that deep-seated neurological defects persist in mice rescued by late activation of Mecp2. To test this possibility, we have quantitatively analysed structural and functional plasticity of the rescued adult male mouse brain. Activation of Mecp2 in ∼70% of neurons reversed many morphological defects in the motor cortex, including neuronal size and dendritic complexity. Restoration of Mecp2 expression was also accompanied by a significant improvement in respiratory and sensory-motor functions, including breathing pattern, grip strength, balance beam and rotarod performance. Our findings sustain the view that MeCP2 does not play a pivotal role in brain development, but may instead be required to maintain full neurological function once development is complete.
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Loss of MeCp2 results in reduced brain weight and thinning of the neocortex in some mouse models.
“Loss of MeCp2 results in reduced brain weight [67, 126], with thinning of the neocortex described in some mouse models [115, 200, 302].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [302]
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- Authors
- Robinson, L., Guy, J., McKay, L., Brockett, E., Spike, R. C., Selfridge, J., De Sousa, D., Merusi, C., Riedel, G., Bird, A., & Cobb, S. R.
- Affiliations
- University of Aberdeen (GB)
- Wellcome Centre for Cell Biology (GB)
- University of Glasgow (GB)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-04-23
- Volume
- 135
- Issue
- 9
- Pages
- 2699-2710
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3437019
- OpenAlex
- W2162467606
- Cited by
- 157
- References
- 54
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 12 · 2023: 5 · 2022: 11 · 2021: 12 · 2020: 13 · 2019: 10 · 2018: 8 · 2017: 15 · 2016: 13 · 2015: 11 · 2014: 9 · 2013: 12 · 2012: 11
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (092076, 091580)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- Rett syndrome, MeCP2, motor cortex, dendritic complexity, neuron size, neuroplasticity, respiratory function, motor function, grip strength, rotarod performance, brain development, X-linked neurodevelopmental disorder
- MeSH terms
- Animals, Behavior, Animal, Cerebral Cortex, Disease Models, Animal, Humans, Neurons, Phenotype, Rett Syndrome, Hand Strength, Gene Silencing, Rotarod Performance Test, Mice, Methyl-CpG-Binding Protein 2
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