TY - JOUR
T1 - Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin
T2 - A model for Duchenne muscular dystrophy
AU - Grady, R. Mark
AU - Teng, Haibing
AU - Nichol, Mia C.
AU - Cunningham, Jeanette C.
AU - Wilkinson, Robert S.
AU - Sanest, Joshua R.
N1 - Funding Information:
We thank M. Elam, S. Weng, C. Chandler, and other members of the laboratory for assistance; R. Crosbie, A. Amalfitano, and J. Chamberlain for help with mdx PCR; G. Shakelford and G. Schnarr for radiographs; and S. Froehner for antiserum to β2-syntrophin. This work was supported by a National Research Service Award (R. Grady), a grant from the Muscular Dystrophy Association of America (J. Sanes), and grants from the National Institutes of Health (J. Sanes and R. Wilkinson).
PY - 1997/8/22
Y1 - 1997/8/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0030848338&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)80533-4
DO - 10.1016/S0092-8674(00)80533-4
M3 - Article
C2 - 9288752
AN - SCOPUS:0030848338
SN - 0092-8674
VL - 90
SP - 729
EP - 738
JO - Cell
JF - Cell
IS - 4
ER -