Progressive Myopenia and Functional Decline in the Winnie Mouse Model of Chronic Colitis

Muscle wasting contributes substantially to inflammatory bowel disease (IBD)-related disability, but its association with colitis severity across disease stages remains poorly characterized. We therefore assessed skeletal muscle mass, fiber morphology, and voluntary wheel-running performance in Winnie mice-a spontaneous Muc2 mutant model of chronic colitis-in separate female and male homozygous mutant and WT littermate cohorts. Assessments were performed at 5 weeks, before overt colitis, and at 15 weeks, in a cohort with more pronounced colitis. Outcomes included disease activity index (DAI), fecal lipocalin-2 (LCN-2), wheel-running metrics, soleus and tibialis anterior mass, and minimal Feret's diameter distributions. At 5 weeks, Winnie mice showed no overt disease activity and no consistent structural muscle deficit. In contrast, the 15-week cohort exhibited marked colitis in both sexes, with increased DAI and LCN-2, reduced voluntary wheel-running performance, lower soleus and tibialis anterior mass, and smaller muscle fiber diameters with left-shifted size distributions. Correlation analyses identified associations between fecal LCN-2, skeletal muscle mass and size, and wheel-running distance and velocity, supporting a link between intestinal inflammation and muscle impairment in this model. These cross-sectional data are consistent with reduced voluntary activity and structural myopathy during progression of spontaneous colitis. The Winnie mouse model therefore provides a clinically relevant preclinical platform to study IBD-associated muscle wasting and its association with intestinal inflammation.