{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:59:46Z","timestamp":1789837186104,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201010\u2010LABX\u201073"],"award-info":[{"award-number":["ANR\u201010\u2010LABX\u201073"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201021\u2010CE13\u20100018"],"award-info":[{"award-number":["ANR\u201021\u2010CE13\u20100018"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disorder characterized by CTG repeat expansion in the 3\u2032 untranslated region of the\n                      <jats:italic>dystrophia myotonica protein kinase<\/jats:italic>\n                      coding gene. The presence of expanded CTG repeats in DMPK mRNAs leads to the sequestration of RNA\u2010binding factors such as the Muscleblind\u2010like (MBNL) proteins, resulting in widespread splicing defects that contribute to progressive muscle weakness and myotonia. Previously, we identified misregulation of\n                      <jats:italic>SORBS1<\/jats:italic>\n                      exon 25 splicing in both DM1 and MBNL1\/2 double\u2010knockout human\u2010induced pluripotent stem cells (hiPSC)\u2010derived skeletal muscle cells, suggesting a potential role in DM1 physiopathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated\n                      <jats:italic>SORBS1<\/jats:italic>\n                      exon 25 splicing misregulation in human skeletal muscle biopsies from DM1 patients and healthy controls. The functional consequence of\n                      <jats:italic>SORBS1<\/jats:italic>\n                      exon 25 exclusion was assessed in mice, zebrafish and hiPSC\u2010derived skeletal muscle cells using an antisense oligonucleotide\u2010mediated exon\u2010skipping strategy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In human congenital DM1 fetal skeletal muscle biopsies,\n                      <jats:italic>SORBS1<\/jats:italic>\n                      exon 25 inclusion was reduced by 52.6\u2009\u00b1\u200910% compared to controls (\n                      <jats:italic>p\u2009&lt;\u20090.001<\/jats:italic>\n                      ). Analysis of RNA sequencing data from the DMseq database further revealed significant misregulation in tibialis anterior biopsies from 40 adult DM1 patients, with a 15.8\u2009\u00b1\u20093.7% decrease in splice inclusion (\n                      <jats:italic>p\u2009&lt;\u20090.0001<\/jats:italic>\n                      ). In mice, forced exclusion of\n                      <jats:italic>Sorbs1<\/jats:italic>\n                      exon 25 led to neuromuscular junction degeneration, with increased denervation (10.5%\u2009\u00b1\u20093.4%,\n                      <jats:italic>p\u2009&lt;\u20090.01<\/jats:italic>\n                      ) and postsynaptic destabilization (5.7%\u2009\u00b1\u20092.5%,\n                      <jats:italic>p\u2009&lt;\u20090.05<\/jats:italic>\n                      ). In zebrafish,\n                      <jats:italic>sorbs1<\/jats:italic>\n                      exon 25 misregulation significantly impaired locomotion, reducing trajectory, distance (57.9%\u2009\u00b1\u200912%,\n                      <jats:italic>p\u2009&lt;\u20090.0001<\/jats:italic>\n                      ) and velocity (14%\u2009\u00b1\u20090.5%,\n                      <jats:italic>p\u2009&lt;\u20090.05<\/jats:italic>\n                      ), while also disrupting acetylcholine receptor cluster morphology. Similarly, forced\n                      <jats:italic>SORBS1<\/jats:italic>\n                      exon 25 exclusion in hiPSC\u2010derived skeletal muscle cells diminished the formation of large acetylcholine receptor clusters upon agrin stimulation by 34%\u2009\n                      <jats:italic>\u00b1<\/jats:italic>\n                      \u20094.5% (\n                      <jats:italic>p\u2009&lt;\u20090.0001<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study identifies\n                      <jats:italic>SORBS1<\/jats:italic>\n                      alternative splicing as an essential MBNL\u2010regulated event during skeletal muscle development, potentially involved in neuromuscular junction formation and maintenance. The aberrant splicing of\n                      <jats:italic>SORBS1<\/jats:italic>\n                      exon 25 in DM1 expands our understanding of how splicing dysregulation compromises neuromuscular system communication, shedding light on the broader impact of mRNA splicing regulation on NMJ integrity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70112","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T08:15:48Z","timestamp":1763453748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alternative Splicing of\n                    <i>SORBS1<\/i>\n                    Affects Neuromuscular Junction Integrity in Myotonic Dystrophy Type 1"],"prefix":"10.1002","volume":"16","author":[{"given":"Caroline","family":"Hermitte","sequence":"first","affiliation":[{"name":"INSERM\/UEPS UMR 861, Paris Saclay University, I\u2010STEM  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