Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: A model for Duchenne muscular dystrophy

R. Mark Grady, Haibing Teng, Mia C. Nichol, Jeanette C. Cunningham, Robert S. Wilkinson, Joshua R. Sanest

Research output: Contribution to journalArticlepeer-review

533 Scopus citations

Abstract

Dystrophin is a cytoskeletal protein of muscle fibers; its loss in humans 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 confined to the postsynaptic membrane at skeletal neuromuscular junctions and has been implicated in synaptic development. Howewer, mice lacking utrophin show only subtle neuromuscular defects. Here, we asked whether the mild phenotypes of the two single mutants reflect compensation between the two proteins. Synaptic development was qualitatively normal in 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 studies of pathogenesis and therapy.

Original languageEnglish
Pages (from-to)729-738
Number of pages10
JournalCell
Volume90
Issue number4
DOIs
StatePublished - Aug 22 1997

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