{
  "abstract": "Loss-of-function variants in SCN2A, which encodes the NaV1.2 sodium channel critical for action potential initiation and backpropagation, are associated with autism spectrum disorder (ASD) and epilepsy. To investigate SCN2A deficiency–related phenotypes, we developed a preclinical mouse model with severe NaV1.2 deficiency, which exhibits robust behavioral abnormalities related to autism and epilepsy. However, the neuronal populations and molecular alterations in the mouse model have not been investigated at single-cell resolution. In this study, we performed single-nucleus RNA sequencing (snRNA-seq) in wild-type (WT), homozygous Scn2a-deficient (HOM), and Scn2a-restored HOM (HOM-FlpO) mice. We then examined how Scn2a expression levels affect cellular composition and gene expression profiles in the medial prefrontal cortex (mPFC), a brain region implicated in ASD. Intriguingly, we observed an increased population of immature GABAergic neurons in adult HOM mice, whereas this population is nearly absent in adult WT mice. Differential expression analysis of GABAergic and glutamatergic neurons across genotypes also revealed widespread changes in genes associated with neurotransmitter regulation and synapse organization. Analysis of the HOM-FlpO data identified genes that were significantly altered in HOM mice and were restored toward WT levels following adult Scn2a restoration. Together, these results indicate that reduced Scn2a expression disrupts global transcriptomic profiles across multiple neural cell types, providing insight into cell–type–specific mechanisms underlying SCN2A-related disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Borch Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN USA",
    "Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN USA",
    "School of Health Sciences, Purdue University, West Lafayette, IN USA",
    "Purdue Institute for Cancer Research, West Lafayette, IN 47907 USA",
    "Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202 USA",
    "Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN USA",
    "Davidson School of Chemical Engineering, West Lafayette, IN USA",
    "Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ye-Eun Yoo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zaiyang Zhang",
      "orcid": "0000-0002-7899-3976"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Purba Mandal"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhengkuan Tang",
      "orcid": "0009-0006-2922-4210"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jingliang Zhang",
      "orcid": "0000-0002-2903-1287"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiaoling Chen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Morgan Robinson"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Muriel Eaton"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Brody Deming"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Manasi Halurkar"
    },
    {
      "affs": [
        3
      ],
      "name": "Harish Kothandaraman",
      "orcid": "0000-0002-0759-4601"
    },
    {
      "affs": [
        4
      ],
      "name": "Luke C. Dabin",
      "orcid": "0000-0001-6365-291X"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Boyu Jiang"
    },
    {
      "affs": [
        5
      ],
      "name": "Hongyu Gao"
    },
    {
      "affs": [
        6
      ],
      "name": "Chongli Yuan"
    },
    {
      "affs": [
        3,
        7
      ],
      "name": "Nadia Lanman"
    },
    {
      "affs": [
        5
      ],
      "name": "Yunlong Liu",
      "orcid": "0000-0002-2699-626X"
    },
    {
      "affs": [
        4
      ],
      "name": "Jungsu Kim",
      "orcid": "0000-0002-6931-8581"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Priyanka Baloni",
      "orcid": "0000-0002-3382-4941"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yang Yang",
      "orcid": "0000-0001-6417-3654"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5fp9bdawvsv6g.bib",
  "cited_by": 0,
  "doi": "10.1038/s41398-026-04348-0",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13713987/",
  "id": "5fp9bdawvsv6g",
  "issns": [
    "2158-3188"
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  "landing_url": "https://doi.org/10.1038/s41398-026-04348-0",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "heading",
      "Article"
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      "openalex",
      "1311|Genetics and Neurodevelopmental Disorders"
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  "pdf_url": null,
  "pmcid": "PMC13713987",
  "pmid": "42946706",
  "published": "2026-07-31",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/5fp9bdawvsv6g.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:21:34Z",
      "native_id": "PMC13713987",
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      "url": "https://doi.org/10.1038/s41398-026-04348-0"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetics and Neurodevelopmental Disorders",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Single-nucleus transcriptomics reveals disrupted pathways in the prefrontal cortex of Scn2a-deficient mice",
  "title_text": "Single-nucleus transcriptomics reveals disrupted pathways in the prefrontal cortex of Scn2a-deficient mice",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:34Z",
  "url": "https://research.draconitic.com/paper/5fp9bdawvsv6g",
  "venue": "Translational Psychiatry",
  "versions": []
}