Utrophin is a regeneration-associated protein transiently present at the sarcolemma of regenerating skeletal muscle fibers in dystrophin-deficient hypertrophic feline muscular dystrophy.
Utrophin, an autosomal homologue of dystrophin, has been suggested as a possible therapeutic replacement of dystrophin in Duchenne or Becker muscular dystrophies (DMD/BMD). We have undertaken this study to examine the expression of utrophin in the skeletal muscle of dystrophin-deficient cats, a spontaneous animal model for dystrophinopathy. Dystrophin was normal in size, but very low in quantity by immunohistochemistry and Western blot. Utrophin was heterogeneously overexpressed at extrajunctional sarcolemma of regenerating muscle fibers, as defined by overexpression of the myogenic markers: vimentin, desmin, and developmental isoform of myosin heavy chain (MHCd). Muscle regeneration occurred in 6 stages as assessed by fiber size, and immunolabeling of desmin, vimentin, and MHCd. Differential developmental patterns of utrophin, alpha-sarcoglycan, and beta-dystroglycan expression were seen with an increase followed by a decrease and with changes in their respective location. These results suggest that utrophin is a regeneration-associated protein. It can functionally replace dystrophin in anchoring dystrophin-associated proteins (DAPs). However, the expression of utrophin and its anchored DAPs is restricted to the period of muscle regeneration and tends to decrease in late stages. This study therefore suggests a novel role of utrophin during skeletal muscle regeneration.
Lin
S
S
Department of Neurology, Faculty of Medicie, University of Berne, Switzerland.
Gaschen
F
F
Burgunder
J M
JM
D000818:Animals; D015153:Blotting, Western; D002415:Cats; D003598:Cytoskeletal Proteins / Q000032:analysis*; D016189:Dystrophin / Q000172:deficiency; D006984:Hypertrophy; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology*; D009124:Muscle Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D012038:Regeneration / Q000502:physiology*; D012508:Sarcolemma / Q000737:chemistry; D013997:Time Factors; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D049411:Utrophin