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Here we show that mice with a cardiomyocyte-specific <jats:italic>Lmna<\/jats:italic> deletion develop cardiac failure and die within 3\u20134 weeks after inducing the mutation. When the same <jats:italic>Lmna<\/jats:italic> mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year. Disruption of SUN1\u2019s function is also accomplished by transducing and expressing a dominant-negative SUN1 miniprotein in <jats:italic>Lmna<\/jats:italic> deficient cardiomyocytes, using the cardiotrophic Adeno Associated Viral Vector 9. The SUN1 miniprotein disrupts binding between the endogenous LINC complex SUN and KASH domains, displacing the cardiomyocyte KASH complexes from the nuclear periphery, resulting in at least a fivefold extension in lifespan. Cardiomyocyte-specific expression of the SUN1 miniprotein prevents cardiomyopathy progression, potentially avoiding the necessity of developing a specific therapeutic tailored to treating each different <jats:italic>LMNA<\/jats:italic> cardiomyopathy-inducing mutation of which there are more than 450.<\/jats:p>","DOI":"10.1038\/s41467-021-24849-4","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T10:05:09Z","timestamp":1628157909000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Disrupting the LINC complex by AAV mediated gene transduction prevents progression of Lamin induced cardiomyopathy"],"prefix":"10.1038","volume":"12","author":[{"given":"Ruth Jinfen","family":"Chai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrikje","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Yiqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0681-2993","authenticated-orcid":false,"given":"Yin Loon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaing Thet","family":"Nyein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6813-7279","authenticated-orcid":false,"given":"Irina","family":"Solovei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan Danh Anh","family":"Luu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavya","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Navasankari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Maric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9417-0830","authenticated-orcid":false,"given":"Lois Yu En","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying Jie","family":"Loh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edita","family":"Aliwarga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason Wen Long","family":"Cheong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Chojnowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9579-9617","authenticated-orcid":false,"given":"Matias Ilmari","family":"Autio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Haiyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth Kian","family":"Boon Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choong Tat","family":"Keng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi Ling","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4774-7959","authenticated-orcid":false,"given":"Wei Leong","family":"Chew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ferenczi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8079-4618","authenticated-orcid":false,"given":"Roger Sik Yin","family":"Foo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4988-536X","authenticated-orcid":false,"given":"Colin L.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"24849_CR1","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/S0140-6736(09)62023-7","volume":"375","author":"JL Jefferies","year":"2010","unstructured":"Jefferies, J. 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