Cited by 39Genetics and Neurodevelopmental DisordersWilliams Syndrome ResearchGenomic variations and chromosomal abnormalities

Early adolescent Rai1 reactivation reverses transcriptional and social interaction deficits in a mouse model of Smith–Magenis syndrome

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Huang, Wei-Hsiang, Wang, David C., Allen, William E., Klope, Matthew, Hu, Hailan, Shamloo, Mehrdad, Luo, Liqun·2018·Proceedings of the National Academy of Sciences

Abstract

Significance: Losing one copy of the RAI1 gene causes Smith–Magenis syndrome (SMS), a neurodevelopmental disorder. Using a newly generated SMS mouse model, this study demonstrates that restoring the Rai1 gene dose in an early postnatal window could repair gene expression and social interaction deficits in this SMS model. The SMS mouse model also showed a reduced density of dendritic spines, anatomical correlates of excitatory synapses, in the prefrontal cortex. Artificial activation of prefrontal cortex neurons partially alleviated the behavioral deficits. These findings suggest that, similar to Rett syndrome, SMS is caused by disruption of a chromatin-modifying gene with reversible developmental phenotypes, highlighting the potential treatment windows in childhood or adolescence.

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Crossref · 10.1073/pnas.1806796115

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  • For some of these monogenic syndromes it has recently been shown that deficits in the structural development of the PFC underlie these problems.

    “For some of these syndromes it has recently been shown that deficits in the structural development of the PFC underlie these problems [281–287].”

    From Development of prefrontal cortex (2022) · cites this paper as [287]

    The Results section ('Reduced Spine Density in Prefrontal Cortex Neurons'; page unavailable) reports reduced dendritic spine density in the medial PFC of one-month-old Rai1-deficient mice. The Discussion (page unavailable) says this structural change *may* contribute to a social-interaction deficit; it does not establish that deficient PFC structural development underlies the problems, or extend that conclusion beyond this mouse model. (LLM, conf=0.87)

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Authors
Huang, W.-H., Wang, D. C., Allen, W. E., Klope, M., Hu, H., Shamloo, M., & Luo, L.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Stanford Medicine (US)
  • Zhejiang University (CN)
Corresponding author
  • Huang, Wei-Hsiang
  • Luo, Liqun
Venue
Proceedings of the National Academy of Sciences
Published
2018-10
Volume
115
Issue
42
Pages
10744-10749
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2895485733
Cited by
39
References
36
Citations by year
2026: 2 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 10 · 2020: 7 · 2019: 1 · 2018: 1 · 2017: 1
FWCI
2.91
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Simons Foundation (SFARI Research Award 345098)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
Smith-Magenis syndrome, RAI1, social interaction deficits, dendritic spines, prefrontal cortex, neurodevelopmental disorders, therapeutic time window, mouse model
MeSH terms
Adolescent, Animals, Disease Models, Animal, Heterozygote, Humans, Interpersonal Relations, Male, Mutation, Phenotype, Social Behavior Disorders, Trans-Activators, Dendritic Spines, Mice, Haploinsufficiency, Smith-Magenis Syndrome

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