The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice
Abstract
Mecp2 is an X-linked gene encoding a nuclear protein that binds specifically to methylated DNA (ref. 1) and functions as a general transcriptional repressor by associating with chromatin-remodeling complexes. Mecp2 is expressed at high levels in the postnatal brain, indicating that methylation-dependent regulation of gene expression may have a crucial role in the mammalian central nervous system. Consistent with this notion is the recent demonstration that MECP2 mutations cause Rett syndrome (RTT, MIM 312750), a childhood neurological disorder that represents one of the most common causes of mental retardation in females. Here we show that Mecp2-deficient mice exhibit phenotypes that resemble some of the symptoms of RTT patients. Mecp2-null mice were normal until 5 weeks of age, when they began to develop disease, leading to death between 6 and 12 weeks. Mutant brains showed substantial reduction in both weight and neuronal cell size, but no obvious structural defects or signs of neurodegeneration. Brain-specific deletion of Mecp2 at embryonic day (E) 12 resulted in a phenotype identical to that of the null mutation, indicating that the phenotype is caused by Mecp2 deficiency in the CNS rather than in peripheral tissues. Deletion of Mecp2 in postnatal CNS neurons led to a similar neuronal phenotype, although at a later age. Our results indicate that the role of Mecp2 is not restricted to the immature brain, but becomes critical in mature neurons. Mecp2 deficiency in these neurons is sufficient to cause neuronal dysfunction with symptomatic manifestation similar to Rett syndrome.
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“Two alleles of Mecp2 are primarily used as mouse models of RTT: Mecp2tm1.1Bird, a null mutation3, and Mecp2tm1.1Jae, which expresses low levels of a truncated protein32.”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [32]
In the citing paper
“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 [67]
Citations
Cites
Generalized lacZ expression with the ROSA26 Cre reporter strain
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Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., & Zoghbi, H. Y. (1999) · Nature Genetics · doi:10.1038/13810 · Cited by 4,990
Nan, X., Ng, H.-H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N., & Bird, A. (1998) · Nature · doi:10.1038/30764 · Cited by 3,440
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
Jones, P. L., Veenstra, G. J. C., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., & Wolffe, A. P. (1998) · Nature Genetics · doi:10.1038/561 · Cited by 2,791
A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome
Guy, J., Hendrich, B., Holmes, M., Martin, J. E., & Bird, A. (2001) · Nature Genetics · doi:10.1038/85899 · Cited by 1,558
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Essential Role for TrkB Receptors in Hippocampus-Mediated Learning
Minichiello, L., Korte, M., Wolfer, D., Kühn, R., Unsicker, K., Cestari, V., Rossi-Arnaud, C., Lipp, H.-P., Bonhoeffer, T., & Klein, R. (1999) · Neuron · doi:10.1016/s0896-6273(00)80853-3 · Cited by 799
(1966) · PubMed · Cited by 708
Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots
Wan, M., Lee, S. S. J., Zhang, X., Houwink-Manville, I., Song, H.-R., Amir, R. E., Budden, S., Naidu, S., Pereira, J. L. P., Lo, I. F. M., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302690 · Cited by 520
Research works printed but not linked: 1
- Rett, A. Uber ein eigenartiges hirnatrophisches Syndrom bei Hyperammonamie im Kindersalter. Wien Med. Wochenschr. 116, 723–726 (1966).
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Cognition and mood-related behaviors in L3mbtl1 null mutant mice
Shen, E. Y., Jiang, Y., Mao, W., Futai, K., Hock, H., & Akbarian, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121252 · Cited by 4
Self-citation
Metadata
- Authors
- Chen, R. Z., Akbarian, S., Tudor, M., & Jaenisch, R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Jaenisch, Rudolf
- Venue
- Nature Genetics
- Published
- 2001-03
- Volume
- 27
- Issue
- 3
- Pages
- 327-331
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1488115555
- Cited by
- 1,275
- References
- 29
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 33 · 2023: 28 · 2022: 40 · 2021: 40 · 2020: 37 · 2019: 41 · 2018: 41 · 2017: 68 · 2016: 68 · 2015: 70 · 2014: 74 · 2013: 77 · 2012: 99
- FWCI
- 28.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- 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
- MeCP2, MeCP2 deficiency, Rett syndrome, DNA methylation, transcriptional repression, chromatin remodeling, neuronal dysfunction, mouse model
- MeSH terms
- Animals, Cell Differentiation, Central Nervous System, Chromosomal Proteins, Non-Histone, Disease Models, Animal, DNA-Binding Proteins, Female, Humans, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Neurons, Phenotype, Repressor Proteins, Rett Syndrome, CpG Islands, Cell Size, Mice, Methyl-CpG-Binding Protein 2
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