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The mechanism by which the toxic RNA causes muscular dystrophy in DM1 is unknown. Dystrophy in DM1 is associated with defective muscle regeneration and repair. Here, we used the BaCl2-induced damage model of muscle injury to study muscle regeneration in the HSALR mouse model of DM1. We have previously shown delayed muscle regeneration and deleterious effects on satellite cell numbers in another mouse model of RNA toxicity using similar experimental approaches. We found that HSALR mice show no apparent deleterious effects on satellite cell number or early markers of muscle regeneration. Further analysis at later time points after damage showed increased numbers of internal nuclei as compared to control mice undergoing the same protocol. Muscle fiber type analysis using immunostaining for type IIA and IIB fibers identified a switch to slower fibers (increased fraction of IIA and reduced fraction of IIB fibers) after regeneration in HSALR mice as compared to regenerated muscle from wildtype mice.<\/jats:p>","DOI":"10.3390\/ijms262210985","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:59:09Z","timestamp":1763027949000},"page":"10985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multiple Defects in Muscle Regeneration in the HSALR Mouse Model of RNA Toxicity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0092-5033","authenticated-orcid":false,"given":"Ramesh S.","family":"Yadava","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-2777","authenticated-orcid":false,"given":"Mira A.","family":"Zineddin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mani S.","family":"Mahadevan","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1045","DOI":"10.1212\/WNL.0000000000011425","article-title":"Population-Based Prevalence of Myotonic Dystrophy Type 1 Using Genetic Analysis of Statewide Blood Screening Program","volume":"96","author":"Johnson","year":"2021","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1159\/000524734","article-title":"Global Prevalence of Myotonic Dystrophy: An Updated Systematic Review and Meta-Analysis","volume":"56","author":"Liao","year":"2022","journal-title":"Neuroepidemiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1126\/science.1546325","article-title":"Myotonic dystrophy mutation: An unstable CTG repeat in the 3\u2032 untranslated region of the gene","volume":"255","author":"Mahadevan","year":"1992","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/0092-8674(92)90154-5","article-title":"Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3\u2032 end of a transcript encoding a protein kinase family member","volume":"68","author":"Brook","year":"1992","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1083\/jcb.128.6.995","article-title":"Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues","volume":"128","author":"Taneja","year":"1995","journal-title":"J. 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