Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice.
Dystrophin-deficient mice (mdx) expressing a truncated (trc) utrophin transgene show amelioration of the dystrophic phenotype. Here we report a multifunctional study demonstrating that trcutrophin expression leads to major improvements of the mechanical performance of muscle (that is, force development, mechanical resistance to forced lengthenings and maximal spontaneous activity) and of the maintenance of the intracellular calcium homeostasis. These are two essential functions of muscle fibers, known to be impaired in mdx mouse muscles and Duchenne muscular dystrophy (DMD) patients. Our results bring strong support to the hypothesis that muscle wasting in dystrophin-deficient DMD patients could be prevented by upregulation of utrophin.
Deconinck
N
N
Département de Physiologie, Université Catholique de Louvain, Brussels, Belgium.
Tinsley
J
J
De Backer
F
F
Fisher
R
R
Kahn
D
D
Phelps
S
S
Davies
K
K
Gillis
J M
JM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016189:Dystrophin / Q000172:deficiency*; D015870:Gene Expression; D015316:Genetic Therapy; D006706:Homeostasis; D007537:Isometric Contraction; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D009119:Muscle Contraction; D009132:Muscles / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000628:therapy; D019076:Transgenes; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008565:Membrane Proteins; C483600:Utrn protein, mouse; D049411:Utrophin; D002118:Calcium