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2026

Dis Model Mech 2026 May 1;19(5):dmm052712. doi: 10.1242/dmm.052712. Epub 2026 Jun 1.

Evaluating skeletal muscle dysfunction and recovery in a zymosan model of critical illness in mice

Amy J Bongetti, Annabel Chee, John H V Nguyen, Jin D Chung, Wenlan Li, Kristy Swiderski, Yasmine Ali Abdelhamid, Olav E Rooyackers, Marissa K Caldow, Gordon S Lynch

Centre for Muscle Research, Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria 3010, Australia. Intensive Care Unit, The Royal Melbourne Hospital, Victoria 3050, Australia. Department of Critical Care, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria 3010, Australia. Perioperative Medicine and Intensive Care, Karolinska University Hospital, 14186 Stockholm, Sweden. Department of Clinical Science, Technology and Intervention, Karolinska Institute, 14152 Stockholm, Sweden.

Service type: Stock strains

Abstract

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.