{
  "abstract": "Mutations in CAV3, encoding caveolin-3, cause caveolinopathies, rare genetic disorders affecting both skeletal and cardiac muscle. Caveolin-3 contributes to T-tubule formation and excitation-contraction coupling. To date, there are no therapy for caveolinopathies. BIN1 (amphiphysin 2), a membrane-shaping protein critical for T-tubule integrity, has shown therapeutic promise in congenital myopathies and heart dysfunction. We evaluated the therapeutic impact of BIN1 overexpression in Cav-3 knockout mice, a model recapitulating key features of human caveolinopathy. We assessed skeletal and cardiac function, T-tubule morphology, mitochondria, and gene expression using histological, physiological, and molecular approaches. Results: We found Cav-3−/− mice displayed skeletal muscle weakness, T-tubule disorganization, and mitochondrial abnormalities, alongside cardiac diastolic dysfunction and myofibrillar disarray. While BIN1 overexpression failed to improve muscle strength, T-tubule structure, or fiber atrophy, it corrected nuclear positioning and partially restored mitochondrial markers in skeletal muscle. In contrast, BIN1 robustly rescued cardiac performance, restoring end-diastolic volume, cardiac output, and sarcomeric integrity. Expression profiling revealed greater dysregulation of excitation-contraction coupling and atrogene pathways in skeletal than in cardiac muscle in Cav-3−/− mice. Cavin-4, a BIN1-interacting protein and caveolar component, was selectively dysregulated in Cav-3−/− muscle, suggesting a mechanistic barrier to BIN1-mediated rescue in this tissue. These findings identify tissue-specific differences in the molecular consequences of caveolin-3 loss and demonstrate that BIN1 overexpression effectively rescues cardiac manifestations of caveolinopathy while only partially ameliorating the associated subcellular defects in skeletal muscle. Our results support BIN1 investigation as a potential target for inherited cardiomyopathies, while highlighting the need for alternative strategies in skeletal muscle.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Alice Moncheaux"
    },
    {
      "name": "Alain Guimond"
    },
    {
      "name": "Coralie Spiegelhalter"
    },
    {
      "name": "Nadia Messaddeq"
    },
    {
      "name": "Chadia Nahy"
    },
    {
      "name": "Jocelyn Laporte"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/40wpqdjvz9x2n.bib",
  "cited_by": 0,
  "doi": "10.1101/2025.09.26.678914",
  "fulltext_url": null,
  "id": "40wpqdjvz9x2n",
  "issns": [
    "0964-6906",
    "1460-2083"
  ],
  "landing_url": "https://univoak.hal.science/hal-05751685v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bbm"
    ],
    [
      "hal",
      "1.sdv.gen"
    ],
    [
      "hal",
      "2.sdv.bbm.bm"
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  "openalex": null,
  "pdf_url": "https://univoak.hal.science/hal-05751685/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-25",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/40wpqdjvz9x2n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "hal-05751685",
      "source": "hal",
      "url": "https://univoak.hal.science/hal-05751685v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "hal:2.sdv.bbm.bm",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.gen",
      "subfield": "genetics-genomics"
    },
    {
      "field": "medicine",
      "origin": "hal:2.sdv.gen.gh",
      "subfield": "human-genetics"
    }
  ],
  "title": "BIN1 overexpression rescues cardiac but not skeletal muscle defects in a mouse model of caveolinopathy",
  "title_text": "BIN1 overexpression rescues cardiac but not skeletal muscle defects in a mouse model of caveolinopathy",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:35Z",
  "url": "https://research.draconitic.com/paper/40wpqdjvz9x2n",
  "venue": "Human Molecular Genetics",
  "versions": []
}