Cited by 40Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchHistone Deacetylase Inhibitors Research

MeCP2 and histone deacetylases 1 and 2 in dorsal striatum collectively suppress repetitive behaviors

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Mahgoub, Melissa, Adachi, Megumi, Suzuki, Kanzo, Liu, Xihui, Kavalali, Ege T, Chahrour, Maria H, Monteggia, Lisa M·2016·Nature Neuroscience

Abstract

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].”

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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
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
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

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