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We investigated whether re-expression of lamin A in cardiomyocytes can rescue the severe phenotype of\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. An adeno-associated virus vector expressing wild-type\n                    <jats:italic>Lmna<\/jats:italic>\n                    (AAV-\n                    <jats:italic>Lmna<\/jats:italic>\n                    \/DJ8) was administered intrathoracically to neonatal mice. Three weeks after injection, treated\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibited robust cardiac\n                    <jats:italic>Lmna<\/jats:italic>\n                    mRNA induction and correct nuclear localization of lamin A protein, indicating efficient cardiotropic gene delivery. Compared with PBS treatment, AAV-\n                    <jats:italic>Lmna<\/jats:italic>\n                    \/DJ8 treatment promoted body weight maintenance, improved left ventricular systolic function, and significantly prolonged survival in\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. To explore the underlying mechanisms, we performed single-nucleus RNA sequencing of cardiomyocytes from wild-type mice, PBS-treated\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, and AAV-\n                    <jats:italic>Lmna<\/jats:italic>\n                    \/DJ8\u2013treated\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. AAV-mediated lamin A re-expression shifted the cardiomyocyte transcriptome toward the wild-type profile, and restored oxidative phosphorylation\u2013related gene programs, which were diminished in untreated\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. These findings demonstrate that targeted re-expression of\n                    <jats:italic>Lmna<\/jats:italic>\n                    partially ameliorates cardiac dysfunction in\n                    <jats:italic>Lmna<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice and highlight the therapeutic potential of\n                    <jats:italic>LMNA<\/jats:italic>\n                    gene replacement for laminopathy-associated cardiomyopathy.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-56394-9","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T21:45:35Z","timestamp":1782769535000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cardiomyocyte lamin A re-expression via AAV-Lmna\/DJ8 ameliorates cardiac dysfunction in Lmna\u2212\/\u2212 mice"],"prefix":"10.1038","volume":"16","author":[{"given":"Miho","family":"Izawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Onoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Jimba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Ioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikako","family":"Katagiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuki","family":"Nakada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seitaro","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shungo","family":"Hikoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"56394_CR1","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/6799","volume":"21","author":"G Bonne","year":"1999","unstructured":"Bonne, G. et al. 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