{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:27:51Z","timestamp":1780583271828,"version":"3.54.1"},"reference-count":43,"publisher":"The Company of Biologists","issue":"5","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":31,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Muscle wasting and weakness are common complications associated with critical illness and admission to the intensive care unit (ICU), which contribute to increased mortality and health deficits post discharge. The mechanisms underlying ICU-acquired muscle weakness (ICU-AW) are incompletely understood, and small-animal models can help address this shortfall and provide experimental platforms for devising therapeutic strategies. We used zymosan treatment to induce wasting and weakness in C57BL\/6J mice and evaluated recovery of hindlimb muscles and diaphragm on day (D)4, D7, D14 and D28 after induction of critical illness, through extensive physiological and immunohistological analyses. Tibialis anterior muscles from zymosan-treated mice exhibited atrophy and functional impairment at D4 and D7, with recovery at D14. In contrast, the diaphragm exhibited a delay in wasting and recovery from critical illness, with muscle fibre atrophy at D28, despite inflammatory cell infiltration from D4 and transient impairments in respiratory function. The zymosan mouse model provides important insights into mechanisms underlying the recovery from wasting and weakness after critical illness to better understand and treat ICU-AW.<\/jats:p>","DOI":"10.1242\/dmm.052712","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:16:32Z","timestamp":1777018592000},"source":"Crossref","is-referenced-by-count":1,"title":["Evaluating skeletal muscle dysfunction and recovery in a zymosan model of critical illness in mice"],"prefix":"10.1242","volume":"19","author":[{"given":"Amy J.","family":"Bongetti","sequence":"first","affiliation":[{"name":"Centre for Muscle Research 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]},{"name":"The University of Melbourne 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel","family":"Chee","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]},{"name":"The University of Melbourne 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H. V.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]},{"name":"The University of Melbourne 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin D.","family":"Chung","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]},{"name":"The University of Melbourne 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlan","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]},{"name":"The University of Melbourne 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy","family":"Swiderski","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]},{"name":"The University of Melbourne 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Ali Abdelhamid","sequence":"additional","affiliation":[{"name":"The Royal Melbourne Hospital 2 Intensive Care Unit , , Victoria 3050 ,","place":["Australia"]},{"name":"The University of Melbourne 3 Department of Critical Care, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olav E.","family":"Rooyackers","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital 4 Perioperative Medicine and Intensive Care , , 14186 Stockholm ,","place":["Sweden"]},{"name":"Karolinska Institutet 5 Department of Clinical Science, Technology and Intervention , , 14152 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa K.","family":"Caldow","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]},{"name":"The University of Melbourne 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9220-9810","authenticated-orcid":false,"given":"Gordon S.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Centre for Muscle Research 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]},{"name":"The University of Melbourne 1 , Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences , , Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"2026060104253111600_DMM052712C1","doi-asserted-by":"publisher","first-page":"C844","DOI":"10.1152\/ajpcell.00402.2005","article-title":"Type II skeletal myofibers possess unique properties that potentiate mitochondrial H2O2 generation","volume":"290","author":"Anderson","year":"2006","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2026060104253111600_DMM052712C2","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1042\/CS20255458","article-title":"Evaluating skeletal muscle wasting and weakness in models of critical illness","volume":"139","author":"Bongetti","year":"2025","journal-title":"Clin. Sci. (Lond)"},{"key":"2026060104253111600_DMM052712C3","doi-asserted-by":"publisher","first-page":"6653","DOI":"10.1113\/JP274792","article-title":"Sensorimotor control of breathing in the mdx mouse model of Duchenne muscular dystrophy","volume":"595","author":"Burns","year":"2017","journal-title":"J. Physiol. Lond."},{"key":"2026060104253111600_DMM052712C4","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.resp.2013.05.012","article-title":"Mechanical ventilation, diaphragm weakness and weaning: a rehabilitation perspective","volume":"189","author":"Daniel Martin","year":"2013","journal-title":"Respir. Physiol. Neurobiol."},{"key":"2026060104253111600_DMM052712C5","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.tim.2011.01.001","article-title":"Cecal ligation and puncture: the gold standard model for polymicrobial sepsis?","volume":"19","author":"Dejager","year":"2011","journal-title":"Trends Microbiol."},{"key":"2026060104253111600_DMM052712C6","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1152\/physrev.00028.2014","article-title":"The sick and the weak: neuropathies\/myopathies in the critically Ill","volume":"95","author":"Friedrich","year":"2015","journal-title":"Physiol. Rev."},{"key":"2026060104253111600_DMM052712C7","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1152\/japplphysiol.00548.2022","article-title":"Hypercapnic signaling influences hypoxic signaling in the control of breathing in C57BL6 mice","volume":"134","author":"Getsy","year":"2023","journal-title":"J. Appl. Physiol."},{"key":"2026060104253111600_DMM052712C8","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1002\/jcsm.12668","article-title":"Impact of prolonged sepsis on neural and muscular components of muscle contractions in a mouse model","volume":"12","author":"Goossens","year":"2021","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"2026060104253111600_DMM052712C9","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1001\/archsurg.1986.01400080039006","article-title":"Multiple-organ failure and sepsis without bacteria. An experimental model","volume":"121","author":"Goris","year":"1986","journal-title":"Arch. Surg."},{"key":"2026060104253111600_DMM052712C10","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1056\/NEJMra2104669","article-title":"Outcomes after critical illness","volume":"388","author":"Herridge","year":"2023","journal-title":"New Engl. J. Med."},{"key":"2026060104253111600_DMM052712C11","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1056\/NEJMoa1011802","article-title":"Functional disability 5 years after acute respiratory distress syndrome","volume":"364","author":"Herridge","year":"2011","journal-title":"New Engl. J. Med."},{"key":"2026060104253111600_DMM052712C12","doi-asserted-by":"publisher","first-page":"e84","DOI":"10.1097\/CCM.0000000000000854","article-title":"Detailed characterization of a long-term rodent model of critical illness and recovery","volume":"43","author":"Hill","year":"2015","journal-title":"Crit. Care Med."},{"key":"2026060104253111600_DMM052712C13","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1002\/mus.21848","article-title":"Impaired respiratory function in mdx and mdx\/utrn+\/- mice","volume":"43","author":"Huang","year":"2011","journal-title":"Muscle Nerve"},{"key":"2026060104253111600_DMM052712C14","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1097\/CCM.0b013e3182676322","article-title":"Cecal ligation and puncture-induced murine sepsis does not cause lung injury","volume":"41","author":"Iskander","year":"2013","journal-title":"Crit. Care Med."},{"key":"2026060104253111600_DMM052712C15","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s10753-014-0034-8","article-title":"Early administration of cisatracurium attenuates sepsis-induced diaphragm dysfunction in rats","volume":"38","author":"Jiang","year":"2015","journal-title":"Inflammation"},{"key":"2026060104253111600_DMM052712C16","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s10020-024-00982-w","article-title":"Post-sepsis chronic muscle weakness can be prevented by pharmacological protection of mitochondria","volume":"30","author":"Kingren","year":"2024","journal-title":"Mol. Med."},{"key":"2026060104253111600_DMM052712C17","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1097\/00003246-199307000-00015","article-title":"Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock","volume":"21","author":"Kreymann","year":"1993","journal-title":"Crit. Care Med."},{"key":"2026060104253111600_DMM052712C18","doi-asserted-by":"publisher","first-page":"e14012","DOI":"10.1111\/apha.14012","article-title":"Slow or fast: Implications of myofibre type and associated differences for manifestation of neuromuscular disorders","volume":"238","author":"Lloyd","year":"2023","journal-title":"Acta Physiol."},{"key":"2026060104253111600_DMM052712C19","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/jcu.22690","article-title":"Alterations in diaphragmatic function assessed by ultrasonography in mechanically ventilated patients with sepsis","volume":"47","author":"Lu","year":"2019","journal-title":"J. Clin. Ultrasound"},{"key":"2026060104253111600_DMM052712C20","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1177\/0885066620949178","article-title":"Incidence, time course and influence on quality of life of intensive care unit-acquired weakness symptoms in long-term intensive care survivors","volume":"36","author":"Meyer-Frie\u00dfem","year":"2021","journal-title":"J. Intensive Care Med."},{"key":"2026060104253111600_DMM052712C21","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1002\/mus.20268","article-title":"Skeletal muscle wasting and contractile performance in septic rats","volume":"31","author":"Minnaard","year":"2005","journal-title":"Muscle Nerve"},{"key":"2026060104253111600_DMM052712C22","doi-asserted-by":"publisher","first-page":"e13668","DOI":"10.1002\/jcsm.13668","article-title":"Local inflammation precedes diaphragm wasting and fibrotic remodelling in a mouse model of pancreatic cancer","volume":"16","author":"Neyroud","year":"2025","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"2026060104253111600_DMM052712C23","doi-asserted-by":"publisher","first-page":"e153944","DOI":"10.1172\/jci.insight.153944","article-title":"Dichloroacetate improves systemic energy balance and feeding behavior during sepsis","volume":"7","author":"Oh","year":"2022","journal-title":"JCI Insight"},{"key":"2026060104253111600_DMM052712C24","doi-asserted-by":"publisher","first-page":"e49920","DOI":"10.7554\/eLife.49920","article-title":"Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model","volume":"8","author":"Owen","year":"2019","journal-title":"eLife"},{"key":"2026060104253111600_DMM052712C25","doi-asserted-by":"publisher","first-page":"529","DOI":"10.3390\/biology12040529","article-title":"Sepsis-like energy deficit is not sufficient to induce early muscle fiber atrophy and mitochondrial dysfunction in a murine sepsis model","volume":"12","author":"Pierre","year":"2023","journal-title":"Biology (Basel)"},{"key":"2026060104253111600_DMM052712C26","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nprot.2008.214","article-title":"Immunodesign of experimental sepsis by cecal ligation and puncture","volume":"4","author":"Rittirsch","year":"2009","journal-title":"Nat. Protoc."},{"key":"2026060104253111600_DMM052712C27","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1042\/cs0870619","article-title":"Prolonged changes in protein and amino acid metabolism after zymosan treatment in rats","volume":"87","author":"Rooyackers","year":"1994","journal-title":"Clin. Sci. (Lond)"},{"key":"2026060104253111600_DMM052712C28","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1042\/cs0920189","article-title":"Contraction failure of skeletal muscle of rats recovering from critical illness","volume":"92","author":"Rooyackers","year":"1997","journal-title":"Clin. Sci. (Lond)"},{"key":"2026060104253111600_DMM052712C29","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13054-021-03535-3","article-title":"Long-term outcomes after critical illness: recent insights","volume":"25","author":"Rousseau","year":"2021","journal-title":"Crit. Care"},{"key":"2026060104253111600_DMM052712C30","doi-asserted-by":"publisher","first-page":"417","DOI":"10.4049\/jimmunol.171.1.417","article-title":"Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A","volume":"171","author":"Sato","year":"2003","journal-title":"J. Immunol."},{"key":"2026060104253111600_DMM052712C31","doi-asserted-by":"publisher","first-page":"C1498","DOI":"10.1152\/ajpcell.00230.2025","article-title":"Cachexia progression differs among mouse models of metastatictriple-negative breast cancer","volume":"329","author":"Saunders","year":"2025","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2026060104253111600_DMM052712C32","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.3389\/fimmu.2019.01427","article-title":"The fluctuations of leukocytes and circulating cytokines in septic humanized mice vary with outcome","volume":"10","author":"Skirecki","year":"2019","journal-title":"Front. Immunol."},{"key":"2026060104253111600_DMM052712C33","doi-asserted-by":"publisher","first-page":"103289","DOI":"10.1016\/j.resp.2019.103289","article-title":"Taurine administration ablates sepsis induced diaphragm weakness","volume":"271","author":"Supinski","year":"2020","journal-title":"Respir. Physiol. Neurobiol."},{"key":"2026060104253111600_DMM052712C34","doi-asserted-by":"publisher","first-page":"e0212880","DOI":"10.1371\/journal.pone.0212880","article-title":"Deletion of suppressor of cytokine signaling 3 (SOCS3) in muscle stem cells does not alter muscle regeneration in mice after injury","volume":"14","author":"Swiderski","year":"2019","journal-title":"PLoS ONE"},{"key":"2026060104253111600_DMM052712C35","doi-asserted-by":"publisher","first-page":"dmm050502","DOI":"10.1242\/dmm.050502","article-title":"The BALB\/c.mdx62 mouse exhibits a dystrophic muscle pathology and is a model of Duchenne muscular dystrophy","volume":"17","author":"Swiderski","year":"2024","journal-title":"Dis. Model. Mech."},{"key":"2026060104253111600_DMM052712C36","doi-asserted-by":"publisher","first-page":"168141","DOI":"10.1016\/j.bbadis.2025.168141","article-title":"FcRn: A novel target to attenuate rheumatoid cachexia in arthritic mice","volume":"1872","author":"Swiderski","year":"2026","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"2026060104253111600_DMM052712C37","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/joim.12104","article-title":"HMGB1 mediates splenomegaly and expansion of splenic CD11b+ Ly-6C(high) inflammatory monocytes in murine sepsis survivors","volume":"274","author":"Vald\u00e9s-Ferrer","year":"2013","journal-title":"J. Intern. Med."},{"key":"2026060104253111600_DMM052712C38","doi-asserted-by":"publisher","first-page":"eadg3894","DOI":"10.1126\/scitranslmed.adg3894","article-title":"Super-relaxed myosins contribute to respiratory muscle hibernation in mechanically ventilated patients","volume":"16","author":"van den Berg","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"2026060104253111600_DMM052712C39","doi-asserted-by":"publisher","first-page":"e1011635","DOI":"10.1371\/journal.ppat.1011635","article-title":"Evidence for vagal sensory neural involvement in influenza pathogenesis and disease","volume":"20","author":"Verzele","year":"2024","journal-title":"PLoS Pathog."},{"key":"2026060104253111600_DMM052712C40","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1097\/01.shk.0000155350.95435.28","article-title":"Zymosan-induced generalized inflammation: experimental studies into mechanisms leading to multiple organ dysfunction syndrome","volume":"23","author":"Volman","year":"2005","journal-title":"Shock"},{"key":"2026060104253111600_DMM052712C41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1113\/jphysiol.1949.sp004363","article-title":"New methods for calculating metabolic rate with special reference to protein metabolism","volume":"109","author":"Weir","year":"1949","journal-title":"J. Physiol. Lond."},{"key":"2026060104253111600_DMM052712C42","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-4804(80)90037-2","article-title":"Sepsis and septic shock--a review of laboratory models and a proposal","volume":"29","author":"Wichterman","year":"1980","journal-title":"J. Surg. Res."},{"key":"2026060104253111600_DMM052712C43","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1097\/MCC.0000000000000650","article-title":"Challenges in conducting long-term outcomes studies in critical care","volume":"25","author":"Wilcox","year":"2019","journal-title":"Curr. Opin. Crit. Care"}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052712\/3695642\/dmm052712.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052712\/3701491\/dmm052712.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052712\/3701491\/dmm052712.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T08:25:37Z","timestamp":1780302337000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/19\/5\/dmm052712\/371850\/Evaluating-skeletal-muscle-dysfunction-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.052712","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"article-number":"dmm052712"}}