MeCP2 and histone deacetylases 1 and 2 in dorsal striatum collectively suppress repetitive behaviors
Open accessAbstract
Class I histone deacetylases (HDACs) Hdac1 and Hdac2 can associate together in protein complexes with transcriptional factors such as methyl-CpG-binding protein 2 (MeCP2). Given their high degree of sequence identity, we examined whether Hdac1 and Hdac2 were functionally redundant in mature mouse brain. We demonstrate that postnatal forebrain-specific deletion of both Hdac1 and Hdac2 in mice impacts neuronal survival and results in an excessive grooming phenotype caused by dysregulation of Sap90/Psd95-associated protein 3 (Sapap3; also known as Dlgap3) in striatum. Moreover, Hdac1- and Hdac2-dependent regulation of Sapap3 expression requires MECP2, the gene involved in the pathophysiology of Rett syndrome. We show that postnatal forebrain-specific deletion of Mecp2 causes excessive grooming, which is rescued by restoring striatal Sapap3 expression. Our results provide new insight into the upstream regulation of Sapap3 and establish the essential role of striatal Hdac1, Hdac2 and MeCP2 for suppression of repetitive behaviors.
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Excessive grooming in Sapap3-KO mice is a motor output caused by the lack of SAPAP3 in the striatum and has compulsive traits since it leads to skin lesions.
“Much attention has been given to excessive grooming in the Sapap3-KO mice, which is a motor output caused by the lack of SAPAP3 in the striatum and has compulsive traits since it leads to skin lesions [9,36].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [36]
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- Authors
- Mahgoub, M., Adachi, M., Suzuki, K., Liu, X., Kavalali, E. T., Chahrour, M. H., & Monteggia, L. M.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Monteggia, Lisa M
- Venue
- Nature Neuroscience
- Published
- 2016-09-26
- Volume
- 19
- Issue
- 11
- Pages
- 1506-1512
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5083208
- OpenAlex
- W2524191147
- Cited by
- 40
- References
- 49
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 5
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Massachusetts Institute of Technology
- National Institute of Mental Health (R01MH081060, R56MH081060, R01MH066198)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- MeCP2, HDAC1, HDAC2, dorsal striatum, repetitive behavior, grooming, neuronal survival, Rett syndrome, protein complex formation
- MeSH terms
- Animals, Behavior, Animal, Central Nervous System, Corpus Striatum, Mice, Transgenic, Nerve Tissue Proteins, Phenotype, Rett Syndrome, Methyl-CpG-Binding Protein 2, Histone Deacetylase 1, Histone Deacetylase 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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