The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes
Open accessAbstract
Mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2), cause Rett syndrome and several neurodevelopmental disorders including cognitive disorders, autism, juvenile-onset schizophrenia and encephalopathy with early lethality. Rett syndrome is characterized by apparently normal early development followed by regression, motor abnormalities, seizures and features of autism, especially stereotyped behaviours. The mechanisms mediating these features are poorly understood. Here we show that mice lacking Mecp2 from GABA (γ-aminobutyric acid)-releasing neurons recapitulate numerous Rett syndrome and autistic features, including repetitive behaviours. Loss of MeCP2 from a subset of forebrain GABAergic neurons also recapitulates many features of Rett syndrome. MeCP2-deficient GABAergic neurons show reduced inhibitory quantal size, consistent with a presynaptic reduction in glutamic acid decarboxylase 1 (Gad1) and glutamic acid decarboxylase 2 (Gad2) levels, and GABA immunoreactivity. These data demonstrate that MeCP2 is critical for normal function of GABA-releasing neurons and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes.
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“One of the best described ASD models, knockout of the gene responsible for Rett syndrome, methyl CpG binding protein 2 (Mecp2), shows repetitive behaviors and stereotypies even if the gene is selectively removed from INs only [54].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [54]
In the citing paper
“several behavioral features characteristic for ASDs, such as repetitive and impaired social behavior”
From Neuronal Dynamics and Neuropsychiatric Disorders: Toward a Translational Paradigm for Dysfunctional Large-Scale Networks (2012) · cites this paper as Chao et al., 2010
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Cites
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
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
Self-citationCre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Srinivas, S., Watanabe, T., Lin, C.-S., William, C. M., Tanabe, Y., Jessell, T. M., & Costantini, F. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-4 · Cited by 3,121
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
Hagberg, B. A., Aicardi, J. F., Dias, K., & Ramos, O. (1983) · Annals of Neurology · doi:10.1002/ana.410140412 · Cited by 1,515
DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation
Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G., & Sun, Y. E. (2003) · Science · doi:10.1126/science.1090842 · Cited by 1,405
Subregion- and Cell Type–Restricted Gene Knockout in Mouse Brain
Tsien, J. Z., Chen, D. F., Gerber, D., Tom, C., Mercer, E. H., Anderson, D. J., Mayford, M., Kandel, E. R., & Tonegawa, S. (1996) · Cell · doi:10.1016/s0092-8674(00)81826-7 · Cited by 1,280
Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice
Chen, R. Z., Akbarian, S., Tudor, M., & Jaenisch, R. (2001) · Nature Genetics · doi:10.1038/85906 · Cited by 1,275
The Story of Rett Syndrome: From Clinic to Neurobiology
Chahrour, M., & Zoghbi, H. Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.001 · Cited by 1,265
Self-citationDerepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2
Chen, W. G., Chang, Q., Lin, Y., Meissner, A., West, A. E., Griffith, E. C., Jaenisch, R., & Greenberg, M. E. (2003) · Science · doi:10.1126/science.1086446 · Cited by 1,232
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Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
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Metadata
- Authors
- Chao, H.-T., Chen, H., Samaco, R. C., Xue, M., Chahrour, M., Yoo, J., Neul, J. L., Gong, S., Lu, H.-C., Heintz, N., Ekker, M., Rubenstein, J. L. R., Noebels, J. L., Rosenmund, C., & Zoghbi, H. Y.
- Affiliations
- Baylor College of Medicine (US)
- Howard Hughes Medical Institute (US)
- University of Ottawa (CA)
- University of California, San Francisco (US)
- Corresponding author
- Rosenmund, Christian
- Zoghbi, Huda Y.
- ORCID
- Venue
- Nature
- Published
- 2010-11
- Volume
- 468
- Issue
- 7321
- Pages
- 263-269
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3057962
- OpenAlex
- W2129032286
- Cited by
- 1,168
- References
- 51
- Citations by year
- 2026: 40 · 2025: 43 · 2024: 51 · 2023: 49 · 2022: 68 · 2021: 101 · 2020: 85 · 2019: 80 · 2018: 68 · 2017: 78 · 2016: 89 · 2015: 81 · 2014: 89 · 2013: 84 · 2012: 97
- FWCI
- 43.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- U.S. Public Health Service (29709)
- National Institute of Mental Health (F31MH078678)
- National Institute of Neurological Disorders and Stroke (K08NS052240, R01NS048884, T32NS043124, R01NS057819)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 024064, R01HD062553, P30HD024064, HD053862)
- 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 › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- Rett syndrome, MeCP2, GABAergic neurons, GABA signalling, repetitive behavior, inhibitory neurotransmission, glutamic acid decarboxylase, presynaptic inhibition, neuropsychiatric disorders, cell type-specific gene deletion, mouse model
- MeSH terms
- Animals, Autistic Disorder, Brain, Compulsive Behavior, Disease Models, Animal, Electroencephalography, gamma-Aminobutyric Acid, Genotype, Glutamate Decarboxylase, Hippocampus, Male, Mice, Transgenic, Neural Inhibition, Synaptic Transmission, Neuronal Plasticity, Neurons, Phenotype, Psychomotor Disorders, Respiration, Reflex, Startle, Signal Transduction, Rett Syndrome, Survival Rate, Self-Injurious Behavior, Presynaptic Terminals, Long-Term Potentiation, Homeodomain Proteins, Stereotypic Movement Disorder, Vesicular Inhibitory Amino Acid Transport Proteins, Mice, Methyl-CpG-Binding Protein 2, Inhibitory Postsynaptic Potentials
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