{
  "abstract": "MEF2C haploinsufficiency syndrome is a severe neurodevelopmental disorder for which no disease-directed treatment is available. We investigated whether neuron-directed adeno-associated virus (AAV) delivery of a functional MEF2C coding sequence during the juvenile period could modify disease-relevant phenotypes in mice heterozygous for a Mef2c exon 4 deletion. Transcript-level analysis identified a brain-enriched MEF2C isoform containing the α1 and β regions (nMEF2C) and a skeletal-muscle-enriched isoform containing α2 but lacking β (mMEF2C). Separate human-synapsin-driven AAV vectors encoding either isoform were administered at postnatal day 28. Control-treated Mef2c heterozygous mice retained baseline sociability but lacked social-novelty preference. Mice treated with either nMEF2C or mMEF2C displayed social-novelty preference and improved selected responses to a new social partner, whereas open-field effects were limited. nMEF2C replacement also corrected dark-phase wakefulness and non-rapid eye movement sleep abnormalities and modified selected state-dependent electroencephalographic ratios, without broadly changing absolute band amplitudes or social-contact electroencephalographic activity. Atlas-based whole-brain mapping revealed region-selective reductions in parvalbumin-immunoreactive profiles; direct statistical evidence of cellular rescue was confined to the secondary motor area after nMEF2C treatment. These findings show that selected MEF2C-dependent phenotypes remain modifiable during the juvenile period and support further optimization of MEF2C gene replacement with respect to isoform, dose, expression control, and cellular targeting.",
  "abstract_shown": true,
  "affiliations": [
    "Songjiang Research Institute, Shanghai Jiao Tong University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Z. Jiao"
    },
    {
      "name": "C. Yu"
    },
    {
      "name": "T. Li"
    },
    {
      "name": "Y. Lai"
    },
    {
      "name": "Y. Yang"
    },
    {
      "name": "Y. Yuan"
    },
    {
      "name": "Y. Zhang"
    },
    {
      "name": "G. Tao"
    },
    {
      "name": "J. Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Z. Qiu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2nxx7rf6a40q0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.14.744746",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.14.744746v2.full",
  "id": "2nxx7rf6a40q0",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.14.744746v2",
  "language": null,
  "licence": "PDM-1.0",
  "licence_label": "Public domain",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/publicdomain/mark/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W7203739185",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.14.744746v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2nxx7rf6a40q0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:37Z",
      "native_id": "10.64898/2026.08.14.744746",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.14.744746v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Juvenile AAV-Mediated MEF2C Gene Replacement Ameliorates Selected Phenotypes in Mef2c-Haploinsufficient Mice",
  "title_text": "Juvenile AAV-Mediated MEF2C Gene Replacement Ameliorates Selected Phenotypes in Mef2c-Haploinsufficient Mice",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:37Z",
  "url": "https://research.draconitic.com/paper/2nxx7rf6a40q0",
  "venue": "bioRxiv",
  "versions": []
}