{
  "abstract": "Genetic loss-of-function (LoF) variants in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been identified as one of the foremost monogenic causes of autism spectrum disorder (ASD). ASD encompasses a broad spectrum of behavioral phenotypes, with impaired sociability as a core characteristic. We have established Scn2a-deficient mice (Scn2agt/gt) to model Scn2a-related ASD and found that this model recapitulates social impairment, exhibiting severe social deficits. Scn2agt/gt mice exhibit neuronal hyperexcitability and a marked global reduction in potassium channel expression, which plays a crucial role in maintaining the resting membrane potential and repolarizing neurons after an action potential. Among these downregulated potassium channels, potassium voltage-gated channel subfamily A member 1 (Kv1.1) was one of the most affected. To explore whether Kv1.1 could be a potential therapeutic target in SCN2A-related ASD, we evaluated the in vivo efficacy of a genetic construct driven by the CaMKII promoter that allows for exogenous expression of human Kv1.1 (hKv1.1) in principal neurons. In Scn2agt/gt mice, we found that hKv1.1 expression normalizes neuronal hyperexcitability. Importantly, doxycycline-induced hKv1.1 expression enhances sociability in Scn2a-deficient mice without influencing social behavior in wild-type mice, and this effect was reversed upon doxycycline withdrawal. Overall, we demonstrate the successful use of an inducible AAV-mediated gene delivery system to supplement hKv1.1 expression to mitigate neuronal hyperexcitability and ameliorate social impairments in a mouse model of SCN2A-related ASD. These findings highlight the contribution of Kv1.1 to SCN2A-associated pathophysiology and its potential as a therapeutic target for severe social deficits.",
  "abstract_shown": true,
  "affiliations": [
    "Purdue University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "B. A. Deming"
    },
    {
      "name": "J. Zhang"
    },
    {
      "name": "I. Vitko"
    },
    {
      "name": "R. P. Gaykema"
    },
    {
      "name": "M. Halurkar"
    },
    {
      "name": "Z. Zhang"
    },
    {
      "name": "A. D. Abeyaratna"
    },
    {
      "name": "R. Ranga"
    },
    {
      "name": "P. Mandal"
    },
    {
      "name": "K. Lund"
    },
    {
      "name": "K. Farmer"
    },
    {
      "name": "D. Ramasamy"
    },
    {
      "name": "E. Perez-Reyes"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8dx6xpa2edbej.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.22.753612",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753612v1.full",
  "id": "8dx6xpa2edbej",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753612v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2805|Autism Spectrum Disorder Research"
    ]
  ],
  "openalex": "W7214209336",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753612v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8dx6xpa2edbej.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:14Z",
      "native_id": "10.64898/2026.09.22.753612",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753612v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Gene therapy with doxycycline-controlled expression of human Kv1.1 reduces neuronal excitability and increases sociability of Scn2a-deficient mice",
  "title_text": "Gene therapy with doxycycline-controlled expression of human Kv1.1 reduces neuronal excitability and increases sociability of Scn2a-deficient mice",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:14Z",
  "url": "https://research.draconitic.com/paper/8dx6xpa2edbej",
  "venue": "bioRxiv",
  "versions": []
}