ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Autism risk gene KMT5B deficiency in prefrontal cortex induces synaptic dysfunction and social deficits via alterations of DNA repair and gene transcription.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Spatially resolved mapping of histones reveals selective neuronal response in Rett syndrome.The FEBS journal · 2026Article
- Disruption of DNA Repair as an Emerging Epigenetic Mechanism Underlying Autism Spectrum Disorder.Current psychiatry reports · 2026Review
- Histone demethylase PHF2 regulates inflammatory genes in Alzheimer's disease.Molecular psychiatry · 2026Article
- KMT5B in Cancerous and Noncancerous Diseases: Clinical and Mechanical Considerations.International journal of medical sciences · 2026Review
- Combined Histological and Proteomic Analysis Reveals Muscle Denervation in KMT5B-Related Neurodevelopmental Disorder: A Case Report.Journal of clinical medicine · 2025Article
- Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.Nature communications · 2025Article
- Bridging Genotype to Phenotype inGenes · 2025Review
- Synaptic Deficits in Adnp-Mutant Mice Are Ameliorated by Histone Demethylase LSD1 Inhibition.Autism research : official journal of the International Society for Autism Research · 2025Article
- Prefrontal cortex excitatory neurons show distinct response to heroin-associated cue and social stimulus after prolonged heroin abstinence in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- Identification of a molecular network regulated by multiple ASD high risk genes.Human molecular genetics · 2024Article
- NovelHeliyon · 2024Article
- Analyses of Conditional Knockout Mice forCells · 2024Article
- Childhood anaesthesia and autism risk: population and murine study.Brain communications · 2024Article
- Structural basis of nucleosomal H4K20 recognition and methylation by SUV420H1 methyltransferase.Cell discovery · 2023Article
- Cerebral organoids as an in vitro model to study autism spectrum disorders.Gene therapy · 2023Review
- IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice.The international journal of neuropsychopharmacology · 2023Article
- Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1.bioRxiv : the preprint server for biology · 2023Article
- Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.Science advances · 2023Article
- Modeling Autism Spectrum Disorders with Induced Pluripotent Stem Cell-Derived Brain Organoids.Biomolecules · 2023Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Large-scale genetic screening has identified KMT5B (SUV420H1), which encodes a histone H4 K20 di- and tri-methyltransferase highly expressed in prefrontal cortex (PFC), as a top-ranking high-risk gene for autism. However, the biological function of KMT5B in the brain is poorly characterized, and how KMT5B deficiency is linked to autism remains largely unknown. Here we knocked down Kmt5b in PFC and examined behavioral and electrophysiological changes, as well as underlying molecular mechanisms. Mice with Kmt5b deficiency in PFC display social deficits, a core symptom of autism, without the alteration of other behaviors. Kmt5b deficiency also produces deficits in PFC glutamatergic synaptic transmission, which is accompanied by the reduced synaptic expression of glutamate receptor subunits and associated proteins. Kmt5b deficiency-induced reduction of H4K20me2 impairs 53BP1-mediated DNA repair, leading to the elevation of p53 expression and its target gene Ddit4 (Redd1), which is implicated in synaptic impairment. RNA-sequencing data indicate that Kmt5b deficiency results in the upregulation of genes enriched in cellular stress response and ubiquitin-dependent protein degradation. Collectively, this study has revealed the functional role of Kmt5b in the PFC, and suggests that Kmt5b deficiency could cause autistic phenotypes by inducing synaptic dysfunction and transcriptional aberration.
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