In vivo In vivo characterization of skeletal muscle function in nebulin‐deficient mice

摘要

Abstract Introduction The conditional nebulin knockout mouse is a new model mimicking nemaline myopathy, a rare disease characterized by muscle weakness and rods within muscle fibers. We investigated the impact of nebulin (NEB) deficiency on muscle function in vivo . Methods Conditional nebulin knockout mice and control littermates were studied at 10 to 12?months. Muscle function (force and fatigue) and anatomy (muscles volume and fat content) were measured in vivo . Myosin heavy chain (MHC) composition and nebulin (NEB) protein expression were assessed by protein electrophoresis. Results Conditional nebulin knockout mice displayed a lower NEB level (?90%) leading to a 40% and 45% reduction in specific maximal force production and muscles volume, respectively. Nebulin deficiency was also associated with higher resistance to fatigue and increased MHC I content. Discussion Adult nebulin‐deficient mice displayed severe muscle atrophy and weakness in vivo related to a low NEB content but an improved fatigue resistance due to a slower contractile phenotype.