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DM1 is multisystemic, with progressive worsening of disease manifestations in affected tissues. Disease progression is attributed to somatic expansion of the CTG repeats with age, resulting in production of CUG\n                    <jats:sub>exp<\/jats:sub>\n                    RNA with enhanced intrinsic toxicity due to increased MBNL sequestration. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM1 mouse model with inducible heart-specific expression of a stable, interrupted 960-CUG-repeat RNA. Sustained CUG\n                    <jats:sub>exp<\/jats:sub>\n                    RNA expression caused progressive cardiac enlargement, contractile dysfunction, conduction delay, myocardial fibrosis, and reduced survival, while MBNL-dependent splicing defects remained static, consistent with the stable repeat length. We also determined the degree of reversibility after different periods of CUG\n                    <jats:sub>exp<\/jats:sub>\n                    RNA expression by shutting off the repeat-containing transgene. Suppression of CUG\n                    <jats:sub>exp<\/jats:sub>\n                    RNA expression rescued cardiac abnormalities, but reversibility declined with longer exposure to the toxic RNA. These findings demonstrate that prolonged expression of stable CUG\n                    <jats:sub>exp<\/jats:sub>\n                    RNA drives progressive cardiac pathology, revealing a mechanism of disease progression in DM1 in addition to somatic expansion.\n                  <\/jats:p>\n                  <jats:p>This manuscript describes a mouse model for myotonic dystrophy type 1 that recapitulates cardiac disease progression, demonstrates reversibility, and highlights the benefits of early intervention<\/jats:p>","DOI":"10.1172\/jci.insight.204278","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T17:19:52Z","timestamp":1773940792000},"source":"Crossref","is-referenced-by-count":2,"title":["Progressive cardiac phenotypes and reduced reversibility from long-term CUGexp RNA expression in a DM1 mouse model"],"prefix":"10.1172","volume":"11","author":[{"given":"Rong-Chi","family":"Hu","sequence":"first","affiliation":[{"name":"Department of 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