Does utrophin expression in muscles of mdx mice during postnatal development functionally compensate for dystrophin deficiency?
We correlated utrophin expression with the physiopathological course in mdx mice. Evolution of the pathology was assessed by monitoring expression of developmental MHC in mdx mice versus control. Utrophin expression is detected by dystrophin/utrophin cross-reacting antibodies and can only be evaluated in mdx mouse muscles (in absence of dystrophin). This protein was expressed at the periphery of all myotubes and myofibers during the first postnatal week. It began declining in fast muscles before the third week and disappeared from the soleus between the 3rd and the 4th week. The decrease was concomitant with a sudden degenerative/regenerative process affecting slow muscle earlier and more massively than fast muscles. The pathological process became stable in all muscle types (except the diaphragm), with greater utrophin expression in the soleus. These results in mdx mice along with observed utrophin expression in severely affected DMD patients suggest that overexpression of utrophin is not enough to explain the stability of regenerated fibers in mdx mice.
INSERM U300, Faculté de Pharmacie, Montpellier, France.
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Robert
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Marini
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D005455:Fluorescent Antibody Technique; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis*; D009132:Muscles / Q000737:chemistry / Q000648:ultrastructure; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009218:Myosins / Q000276:immunology; D049411:Utrophin
D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008565:Membrane Proteins; D009124:Muscle Proteins; C483600:Utrn protein, mouse; D049411:Utrophin; D009218:Myosins