Cited by 89Genetics and Neurodevelopmental DisordersDown syndrome and intellectual disability researchGenomics and Rare Diseases

Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition

Deliu, Elena, Arecco, Niccolò, Morandell, Jasmin, Dotter, Christoph P., Contreras, Ximena, Girardot, Charles, Käsper, Eva-Lotta, Kozlova, Alena +4 more·2018·Nature Neuroscience

Abstract

SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder.

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Crossref · 10.1038/s41593-018-0266-2

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  • Loss of SETD5 results in activation of neuronal genes and Wnt signaling in mouse fetal tissue and human cells.

    “Recent studies of SETD5 in mouse fetal tissue and human cells have reported that loss of SETD5 results in the activation of neuronal genes and Wnt signaling (Deliu et al., 2018).”

    From Getting to the cores of autism (2019) · cites this paper as Deliu et al., 2018

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Authors
Deliu, E., Arecco, N., Morandell, J., Dotter, C. P., Contreras, X., Girardot, C., Käsper, E.-L., Kozlova, A., Kishi, K., Chiaradia, I., Noh, K.-M., & Novarino, G.
Affiliations
  • Institute of Science and Technology Austria (AT)
  • Heidelberg University (DE)
  • European Molecular Biology Laboratory (DE)
Corresponding author
  • Noh, Kyung-Min
  • Novarino, Gaia
Venue
Nature Neuroscience
Published
2018-11-19
Volume
21
Issue
12
Pages
1717-1727
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2900030163
Cited by
89
References
85
Citations by year
2026: 9 · 2025: 6 · 2024: 16 · 2023: 14 · 2022: 14 · 2021: 12 · 2020: 10 · 2019: 7 · 2018: 1
FWCI
4.59
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
SETD5, haploinsufficiency, intellectual disability, autism spectrum disorder, brain-to-body weight ratio, neural crest defects, long-term potentiation, ultrasonic vocalizations, behavioral inflexibility, postsynaptic density proteins, gene transcription, HDAC3, Paf1 complex, developmental gene expression, cognition
MeSH terms
Animals, Behavior, Animal, Brain, Cognition, Methyltransferases, RNA Polymerase II, Vocalization, Animal, Gene Expression, Long-Term Potentiation, Mice, Knockout, Gene Expression Regulation, Developmental, Haploinsufficiency

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