{
  "abstract": "Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disorder characterized by arrhythmias and fibrofatty myocardial remodeling, often leading to heart failure and sudden cardiac death. Mutations in plakophilin-2 (PKP2) represent the most prevalent genetic cause of ACM. Here, we establish zebrafish (Danio rerio) as a complementary vertebrate model for PKP2 mutation-based ACM. Comparative single-cell RNA-seq analyses revealed distinct cardiac expression patterns of PKP2 and its homologs across species. Using CRISPR-Cas9, we generated two truncating mutations in zebrafish pkp2, resulting in frameshifts and premature terminations (p.Glu250Glyfs∗17 and p.Glu31Glyfs∗72, respectively). Mutant zebrafish exhibited impaired cardiac contractility, arrhythmias, lipid accumulation on the ventricular surface, ultrastructural abnormalities of intercalated discs, and increased susceptibility to swimming exercise-induced sudden death. Transcriptomic analyses identified transcriptional alterations in genes involved in muscle contraction and lipid metabolism. Together, these data establish zebrafish as a useful complementary vertebrate model for studying PKP2-based ACM and gene-environment interactions underlying disease progression.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Yuting Liu"
    },
    {
      "name": "Yujuan Niu"
    },
    {
      "name": "Yajie Jiang"
    },
    {
      "name": "Taiwei Ma"
    },
    {
      "name": "Peng Yang"
    },
    {
      "name": "Wenyu Ma"
    },
    {
      "name": "Shuai Liu"
    },
    {
      "name": "Yuehang Xu"
    },
    {
      "name": "Hui Xin"
    },
    {
      "name": "Hong Zhang"
    },
    {
      "name": "Chuanhong Wu"
    },
    {
      "name": "Zhiqiang Li"
    },
    {
      "name": "Yuanchao Sun"
    },
    {
      "name": "Yonghe Ding",
      "orcid": "0000-0002-4531-1721"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8zjw8rjpqg13v.bib",
  "cited_by": 0,
  "doi": "10.1016/j.isci.2026.117755",
  "fulltext_url": "https://europepmc.org/articles/PMC13694902",
  "id": "8zjw8rjpqg13v",
  "issns": [
    "2589-0042"
  ],
  "landing_url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03136-6",
  "language": "eng",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Cardiovascular medicine"
    ],
    [
      "heading",
      "Developmental biology"
    ],
    [
      "heading",
      "Molecular Genetics"
    ],
    [
      "openalex",
      "2705|Cardiac electrophysiology and arrhythmias"
    ]
  ],
  "openalex": "W7221751707",
  "pdf_url": "https://europepmc.org/articles/PMC13694902?pdf=render",
  "pmcid": "PMC13694902",
  "pmid": "42927219",
  "published": "2026-10-14",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/8zjw8rjpqg13v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:16Z",
      "native_id": "10.1016/j.isci.2026.117755",
      "source": "feed-cell",
      "url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03136-6"
    },
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1016/j.isci.2026.117755",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2589004226031366"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42927219",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42927219"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Developmental biology",
      "subfield": "developmental-biology"
    },
    {
      "field": "medicine",
      "origin": "heading:Cardiovascular medicine",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Stable truncating mutations in plakophilin-2 induce arrhythmogenic cardiomyopathy-like phenotypes in adult zebrafish",
  "title_text": "Stable truncating mutations in plakophilin-2 induce arrhythmogenic cardiomyopathy-like phenotypes in adult zebrafish",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/8zjw8rjpqg13v",
  "venue": "iScience",
  "versions": []
}