SKELETAL AND CARDIAC MYOPATHIES IN MICE LACKING UTROPHIN AND DYSTROPHIN - A MODEL FOR DUCHENNE MUSCULAR-DYSTROPHY

Dystrophin is a cytoskeletal protein of muscle fibers; its toss in hum ans leads to Duchenne muscular dystrophy, an inevitably fatal wasting of skeletal and cardiac muscle. mdx mice also lack dystrophin, but are only mildly dystrophic. Utrophin, a homolog of dystrophin, is confine d to the postsynaptic membrane at skeletal neuromuscular junctions and has been implicated in synaptic development. However, mice lacking ut rophin show only subtle neuromuscular defects. Here, we asked whether the mild phenotypes of the two single mutants reflect compensation bet ween the two proteins. Synaptic development was qualitatively normal i n double mutants, but dystrophy was severe and closely resembled that seen in Duchenne. Thus, utrophin attenuates the effects of dystrophin deficiency, and the double mutant may provide a useful model for studi es of pathogenesis and therapy.