{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:11:29Z","timestamp":1791645089021,"version":"4.3.4"},"reference-count":96,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Starting Package Fondazione Cariparo","award":["C93C22008360007"],"award-info":[{"award-number":["C93C22008360007"]}]},{"name":"Starting Package Fondazione Cariparo","award":["101115536"],"award-info":[{"award-number":["101115536"]}]},{"DOI":"10.13039\/501100000780","name":"EIC Pathfinder IMPACT","doi-asserted-by":"publisher","award":["C93C22008360007"],"award-info":[{"award-number":["C93C22008360007"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"EIC Pathfinder IMPACT","doi-asserted-by":"publisher","award":["101115536"],"award-info":[{"award-number":["101115536"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Arrhythmogenic cardiomyopathy (ACM) is a rare genetic cardiac disease characterized by the progressive substitution of myocardium with fibro-fatty tissue. Clinically, ACM shows wide variability among patients; symptoms can include syncope and ventricular tachycardia but also sudden death, with the latter often being its sole manifestation. Approximately half of ACM patients have been found with variations in one or more genes encoding cardiac intercalated discs proteins; the most involved genes are plakophilin 2 (PKP2), desmoglein 2 (DSG2), and desmoplakin (DSP). Cardiac intercalated discs provide mechanical and electro-metabolic coupling among cardiomyocytes. Mechanical communication is guaranteed by the interaction of proteins of desmosomes and adheren junctions in the so-called area composita, whereas electro-metabolic coupling between adjacent cardiac cells depends on gap junctions. Although ACM has been first described almost thirty years ago, the pathogenic mechanism(s) leading to its development are still only partially known. Several studies with different animal models point to the involvement of the Wnt\/\u03b2-catenin signaling in combination with the Hippo pathway. Here, we present an overview about the existing murine models of ACM harboring variants in intercalated disc components with a particular focus on the underlying pathogenic mechanisms. Prospectively, mechanistic insights into the disease pathogenesis will lead to the development of effective targeted therapies for ACM.<\/jats:p>","DOI":"10.3390\/ijms25116208","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T05:59:42Z","timestamp":1717567182000},"page":"6208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Animal Models and Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy Associated with Pathogenic Variants in Intercalated Disc Genes"],"prefix":"10.3390","volume":"25","author":[{"given":"Sara","family":"Vencato","sequence":"first","affiliation":[{"name":"Department of Biology, University of Padova, Via U. Bassi 58\/B, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Romanato","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, Via U. Bassi 58\/B, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3884-8843","authenticated-orcid":false,"given":"Alessandra","family":"Rampazzo","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, Via U. Bassi 58\/B, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Calore","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, Via U. Bassi 58\/B, 35121 Padova, Italy"},{"name":"Department of Molecular Genetics, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6211 LK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s11897-021-00532-z","article-title":"Insights into Genetics and Pathophysiology of Arrhythmogenic Cardiomyopathy","volume":"18","author":"Gerull","year":"2021","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/nrcardio.2011.173","article-title":"Pathophysiology of arrhythmogenic cardiomyopathy","volume":"9","author":"Basso","year":"2012","journal-title":"Nat. Rev. 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