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]
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“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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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
Swerdlow, N. R., Geyer, M. A., & BRAFF, D. L. (2001) · Psychopharmacology · doi:10.1007/s002130100799 · Cited by 1,053
Akbarian, S. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950160008002 · Cited by 1,002
A Neuroligin-3 Mutation Implicated in Autism Increases Inhibitory Synaptic Transmission in Mice
Tabuchi, K., Blundell, J., Etherton, M. R., Hammer, R. E., Liu, X., Powell, C. M., & Südhof, T. C. (2007) · Science · doi:10.1126/science.1146221 · Cited by 997
Gong, S., Doughty, M., Harbaugh, C. R., Cummins, A., Hatten, M. E., Heintz, N., & Gerfen, C. R. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2707-07.2007 · Cited by 977
Self-citationShahbazian, M. D., Young, J. I., Yuva‐Paylor, L. A., Spencer, C. M., Antalffy, B. A., Noebels, J. L., Armstrong, D. L., Paylor, R. E., & Zoghbi, H. Y. (2002) · Neuron · doi:10.1016/s0896-6273(02)00768-7 · Cited by 772
Self-citationThe Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus
Monory, K., Massa, F., Egertová, M., Eder, M., Blaudzun, H., Westenbroek, R., Kelsch, W., Jacob, W., Marsch, R., Ekker, M., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.006 · Cited by 706
Self-citationNeuronal MeCP2 Is Expressed at Near Histone-Octamer Levels and Globally Alters the Chromatin State
Skene, P. J., Illingworth, R. S., Webb, S., Kerr, A. R. W., James, K. D., Turner, D. J., Andrews, R., & Bird, A. P. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.030 · Cited by 688
Chaudhry, F. A., Reimer, R. J., Bellocchio, E. E., Danbolt, N. C., Osen, K. K., Edwards, R. H., & Storm‐Mathisen, J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09733.1998 · Cited by 640
Dani, V. S., Chang, Q., Maffei, A., Turrigiano, G. G., Jaenisch, R., & Nelson, S. B. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506071102 · Cited by 639
Regulation of γ‐Aminobutyric Acid Synthesis in the Brain
Martin, D. L., & Rimvall, K. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03165.x · Cited by 615
MeCP2 Controls Excitatory Synaptic Strength by Regulating Glutamatergic Synapse Number
Chao, H.-T., Zoghbi, H. Y., & Rosenmund, C. (2007) · Neuron · doi:10.1016/j.neuron.2007.08.018 · Cited by 511
Self-citationPharmacotherapy for cognitive impairment in a mouse model of Down syndrome
Fernandez, F., Morishita, W., Zuniga, E., Nguyen, J., Blank, M., Malenka, R. C., & Garner, C. C. (2007) · Nature Neuroscience · doi:10.1038/nn1860 · Cited by 509
Fatemi, S. H., Halt, A. R., Stary, J. M., Kanodia, R., Schulz, S. C., & Realmuto, G. R. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01430-0 · Cited by 500
Specific mutations in Methyl-CpG-Binding Protein 2 confer different severity in Rett syndrome
Neul, J. L., Fang, P., Barrish, J., Lane, J., Caeg, E. B., Smith, E. O., Zoghbi, H., Percy, A., & Glaze, D. G. (2008) · Neurology · doi:10.1212/01.wnl.0000291011.54508.aa · Cited by 498
Self-citationNon–cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology
Ballas, N., Lioy, D. T., Grunseich, C., & Mandel, G. (2009) · Nature Neuroscience · doi:10.1038/nn.2275 · Cited by 466
Neurofibromin Regulation of ERK Signaling Modulates GABA Release and Learning
Cui, Y., Costa, R. M., Murphy, G. G., Elgersma, Y., Zhu, Y., Gutmann, D. H., Parada, L. F., Módy, I., & Silva, A. J. (2008) · Cell · doi:10.1016/j.cell.2008.09.060 · Cited by 445
Clinical manifestations and stages of rett syndrome
Hagberg, B. (2002) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.10020 · Cited by 416
Yasui, D. H., Peddada, S., Bieda, M. C., Vallero, R. O., Hogart, A., Nagarajan, R. P., Thatcher, K. N., Farnham, P., & LaSalle, J. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707442104 · Cited by 388
A shared vesicular carrier allows synaptic corelease of GABA and glycine
Wojcik, S. M., Katsurabayashi, S., Guillemin, I., Friauf, E., Rosenmund, C., Brose, N., & Rhee, J.-S. (2006) · Neuron · doi:10.1016/j.neuron.2006.04.016 · Cited by 374
Self-citationFatemi, S. H., Stary, J. M., Earle, J. A., Araghi‐Niknam, M., & Eagan, E. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.02.017 · Cited by 304
Minimal aberrant behavioral phenotypes of neuroligin‐3 R451C knockin mice
Chadman, K. K., Gong, S., Scattoni, M. L., Boltuck, S. E., Gandhy, S. U., Heintz, N., & Crawley, J. N. (2008) · Autism Research · doi:10.1002/aur.22 · Cited by 292
Self-citationRett Syndrome Astrocytes Are Abnormal and Spread MeCP2 Deficiency through Gap Junctions
Maezawa, I., Swanberg, S. E., Harvey, D. J., LaSalle, J. M., & Jin, L. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0324-09.2009 · Cited by 289
Kohwi, M., Petryniak, M. A., Long, J. E., Ekker, M., Obata, K., Yanagawa, Y., Rubenstein, J. L. R., & Álvarez-Buylla, A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0254-07.2007 · Cited by 270
Self-citationSamaco, R. C., Mandel‐Brehm, C., Chao, H.-T., Ward, C. S., Fyffe-Maricich, S. L., Ren, J. T., Hyland, Κ., Christina Thaller, B., Maricich, S. M., Humphreys, P., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912257106 · Cited by 259
Self-citationFyffe, S. L., Neul, J. L., Samaco, R. C., Chao, H.-T., Ben-Shachar, S., Moretti, P., McGill, B. E., Goulding, E. H., Sullivan, E., Tecott, L. H., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.07.030 · Cited by 254
Self-citationGemelli, T., Berton, O., Nelson, E. D., Perrotti, L. I., Jaenisch, R., & Monteggia, L. M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.07.025 · Cited by 244
Identification of MeCP2 mutations in a series of females with autistic disorder
Carney, R. M., Wolpert, C. M., Ravan, S. A., Shahbazian, M. D., Ashley‐Koch, A. E., Cuccaro, M. L., Vance, J. M., & Pericak‐Vance, M. A. (2003) · Pediatric Neurology · doi:10.1016/s0887-8994(02)00624-0 · Cited by 237
Early Defects of GABAergic Synapses in the Brain Stem of a MeCP2 Mouse Model of Rett Syndrome
Medrihan, L., Tantalaki, E., Aramuni, G., Sargsyan, V., Dudanova, I., Missler, M., & Zhang, W. (2007) · Journal of Neurophysiology · doi:10.1152/jn.00826.2007 · Cited by 237
Addington, A. M., Gornick, M., Duckworth, J., Sporn, A. L., Gogtay, N., Bobb, A., GREENSTEIN, D. K., Lenane, M., Gochman, P., Baker, N., et al. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001599 · Cited by 207
Samaco, R. C., Fryer, J. D., Ren, J. T., Fyffe-Maricich, S. L., Chao, H.-T., Sun, Y., Greer, J. J., Zoghbi, H. Y., & Neul, J. L. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn062 · Cited by 189
Self-citationWeese‐Mayer, D. E., Lieske, S. P., Boothby, C. M., Kenny, A. S., Bennett, H., Silvestri, J. M., & Ramirez, J. (2006) · Pediatric Research · doi:10.1203/01.pdr.0000238302.84552.d0 · Cited by 175
Zhang, L., He, J., Jugloff, D. G. M., & Eubanks, J. H. (2007) · Hippocampus · doi:10.1002/hipo.20389 · Cited by 154
Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome
Lam, C. W., YEUNG, W.-L., KO, C.-H., POON, P. M. K., TONG, S.-F., CHAN, K.-Y., Lo, I. F. M., CHAN, L. Y. S., HUI, J., WONG, V., et al. (2000) · Journal of Medical Genetics · doi:10.1136/jmg.37.12.e41 · Cited by 150
Adachi, M., Autry, A. E., Covington, H. E., & Monteggia, L. M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4225-08.2009 · Cited by 135
Klauck, S. M., Lindsay, S., Beyer, K. S., Splitt, M. P., Burn, J., & Poustka, A. (2002) · The American Journal of Human Genetics · doi:10.1086/339553 · Cited by 126
Dani, V. S., & Nelson, S. B. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1019-09.2009 · Cited by 124
Autonomic dysregulation in young girls with Rett Syndrome during nighttime in‐home recordings
Weese‐Mayer, D. E., Lieske, S. P., Boothby, C. M., Kenny, A. S., Bennett, H., & Ramirez, J. (2008) · Pediatric Pulmonology · doi:10.1002/ppul.20866 · Cited by 124
MECP2 Mutation in a Boy With Language Disorder and Schizophrenia
Cohen, D., Lazar, G., Couvert, P., DESPORTES, V., Lippe, D., Mazet, P., & Héron, D. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.1.148-a · Cited by 104
The Overlapping Spectrum of Rett and Angelman Syndromes: A Clinical Review
Jedele, K. B. (2007) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2007.07.002 · Cited by 56
Lundorf, M. D., Buttenschøn, H. N., Foldager, L., Blackwood, D. H. R., Muir, W. J., Murray, V., Pelosi, A. J., Kruse, T. A., Ewald, H., & Mors, O. N. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30137 · Cited by 53
Rett Syndrome: Pathogenesis, Diagnosis, Strategies, Therapies, and Future Research Directions
Deidrick, K. M., Percy, A. K., Schanen, N. C., Mamounas, L. A., & Maria, B. L. (2005) · Journal of Child Neurology · doi:10.1177/08830738050200090201 · Cited by 12
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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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