IMPAIRED RESPIRATORY FUNCTION IN mdx AND mdx/utrn+/― MICE

Muscle fibrosis is a prominent pathological feature that directly causes muscle dysfunction in Duchenne muscular dystrophy (DMD). The DMD mouse models, mdx mice and mdx mice with haploinsufficiency of the utrophin gene (mix/ utrn+/―), display progressive diaphragm fibrosis. We performed unrestrained whole-body plethysmography (WBP) in mdx and mdx/utrn+/― mice, and compared them with wild-type controls. Respiratory function gauged by respiratory frequency, tidal volume, minute volume, peak inspiratory flow, and peak expiratory flow was significantly impaired in the mdx mice. Consistent with more severe diaphragm fibrosis in the mdx/utrn+/― mice, respiratory impairment was worse than in mdx mice at 6 months. WBP is useful for monitoring in vivo respiratory function of mdx and mdx/utrn+/ mice, and it may serve as an outcome measurement for therapies that target diaphragm fibrosis. The mdx/ utrn+/― mouse model may be better than the mdx model for testing antifibrotic therapies, especially at the severe stage.