A Non-invasive Mouse Model That Recapitulates Disuse-Induced Muscle Atrophy in Immobilized Patients

Disuse muscle atrophy occurs consequent to prolonged limb immobility or bed rest, which represents an unmet medical need. As existing animal models of limb immobilization often cause skin erosion, edema, and other untoward effects, we here report an alternative method via thermoplastic immobilization of hindlimbs in mice. While significant decreases in the weight and fiber size were noted after 7 days of immobilization, no apparent skin erosion or edema was found. To shed light onto the molecular mechanism underlying this muscle wasting, we performed the next-generation sequencing analysis of gastrocnemius muscles from immobilized versus non-mobilized legs. Among a total of 55,487 genes analyzed, 787 genes were differentially expressed (> 4-fold; 454 and 333 genes up- and down-regulated, respectively), which included genes associated with muscle tissue development, muscle system process, protein digestion and absorption, and inflammation-related signaling. To the best our knowledge, this is the first study that used RNA-seq to reveal changes in the skeletal muscle transcriptome profiling in response to disuse atrophy without denervation. From a clinical perspective, this model may help understand the molecular/cellular mechanism that drives muscle disuse and identify therapeutic strategies for this debilitating disease. Overall design: Animals: C57Bl/6 male mice, eight -weeks old. Grouping: NC, muscle from naïve mice; Dis, muscle from immobilized leg; Con, muscle from immobilized leg. Treatment: right immobilize hindlimb for 7 days with thermoplastic bandage. Tissue: gastrocnemius. Muscle. Analysis: next-generation sequencing