{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:03:18Z","timestamp":1784887398071,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Muscle atrophy occurs during physiological (i.e., fasting) and pathological conditions (i.e., cancer) and anticipates death. Since not all patients will undergo muscle wasting, it would be highly useful to identify them soon to intervene early. We aim to generate a reporter system to follow only pathological, but not physiological, muscle wasting through in\u00a0vivo imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Comparing the upstream non\u2010coding regions of a subset of atrophy\u2010related genes or atrogenes, using the\n                      <jats:italic>MuRF1<\/jats:italic>\n                      promoter as a backbone, we cloned various promoters upstream of\n                      <jats:italic>Firefly Luciferase<\/jats:italic>\n                      . The best hits selected in\u00a0vitro were further compared in in\u00a0vivo imaging if able to sense early atrophy induced by MCG101 sarcoma or sciatic nerve resection through plasmid electroporation or AAV9 injections. The best promoter was used to generate the reporter mouse MyoRep, expressing the cassette in all skeletal and cardiac muscles using the loxP system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Luciferase assays showed that only the newly generated promoters of MuRF1, one containing glucocorticoid\u2010responsive elements or GRE (TWIST) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01, 1.7 FC) and a GRE\u2010less promoter (GREDEL) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.0001, 1.6 FC), discriminated the supernatants from cachectic tumoural cells (C26) from non\u2010cachectic ones (4T1). Comparing both reporters electroporated in leg muscles, we found that GREDEL, but not TWIST, anticipated atrophy by 6\u2009days in MCG101 carriers (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05) and by 8\u2009days upon denervation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05), recapitulating MuRF1 inductions. TWIST, but not GREDEL, drove an undesirable bioluminescent signal in\u00a0vitro to dexamethasone (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.001, 1.5 FC) and in\u00a0vivo upon fasting (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0553, 3 FC). GREDEL\u2010carrying AAV9 injected in the legs of Apc\n                      <jats:sup>Min\/+<\/jats:sup>\n                      mice unraveled sex\u2010different cachexia and anticipated body emaciation by 1\u2009week (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.001, 3.7 FC). GREDEL was then used to generate the MyoRep mouse. Dorsal view of bioluminescent signal of MCG101\u2010carrying MyoRep mice increased already 6\u2009days from tumour injection (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01, 1.7 FC) when tumour is still unpalpable. Denervated MyoRep mice emitted a signal already 1\u2009day after surgery (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05, 1.4 FC), anticipating atrophy. Male Apc\n                      <jats:sup>Min\/+<\/jats:sup>\n                      mice display less musclin in their muscles (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05, 0.4 FC) and plasma (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01, 0.6 FC). Such mice, when expressing MyoRep in their muscle legs, were given the anti\u2010catabolic myokine musclin. The emitted signal was decreased by 30% 3\u2009weeks after musclin\u2010AAV9 administration (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05), supporting MyoRep useful to test anti\u2010atrophic drugs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Since MyoRep detects only pathological atrophy anticipating wasting, it represents an unprecedented tool to predict it early in diseases with local or systemic atrophy. It could also be useful to identify early biomarkers of atrophy and new drugs at once.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70296","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:48:26Z","timestamp":1778644106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MyoRep: A Novel Reporter System to Detect Early Muscle Atrophy In\u00a0Vitro and In\u00a0Vivo"],"prefix":"10.1002","volume":"17","author":[{"given":"Andrea D.","family":"Re Cecconi","sequence":"first","affiliation":[{"name":"Department of Neuroscience Mario Negri Institute for Pharmacological Research IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Direzione Servizi per la Ricerca\u2014Settore Animal Care Unit University of Milan  Milan 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