Dystrophin is replaced by utrophin in frog heart; implications for muscular dystrophy.
The possibility of using utrophin upregulation as a treatment for dystrophin-deficient muscular dystrophies has focused attention on the question of how many of dystrophin's various functions can be performed by the closely-related protein, utrophin. In Xenopus heart, little or no dystrophin was found on Western blots but the dystrophin-related protein, utrophin, was abundant. This utrophin was shown by immunofluorescence microscopy to be associated with cardiac muscle membranes and its distribution was similar to that of dystrophin in rabbit heart. The utrophin distribution pattern in the frog heart was shared by beta-dystroglycan, a transmembrane protein responsible for localizing both dystrophin and utrophin at cell membranes. The results suggest that utrophin in Xenopus heart can perform similar functions to dystrophin in mammalian heart, lending further support to the possibility of utrophin upregulation therapy in muscular dystrophy. In skeletal muscle, however, Xenopus resembles mammals in expressing dystrophin at the sarcolemma and very little utrophin.
Morris
G E
GE
MRIC Biochemistry Group, N.E. Wales Institute, Wrexham, UK. morrisge@newi.ac.uk
D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016189:Dystrophin / Q000172:deficiency*; D008565:Membrane Proteins / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009136:Muscular Dystrophies / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D049411:Utrophin; D014982:Xenopus laevis
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008565:Membrane Proteins; D049411:Utrophin