Force impairment in calpain 3-deficient mice is not correlated with mechanical disruption.
Defects in human calpain 3 are responsible for limb-girdle muscular dystrophy type 2A, an autosomal-recessive disorder characterized mainly by late-onset proximal muscular atrophy. A corresponding murine model has previously been generated by gene targeting. In this report, muscular activity of calpain 3-deficient (capn3(-/-)) mice was evaluated at different ages. Growth curves showed a progressive global muscular atrophy. Histological examination throughout the lifespan of mice confirmed the dystrophic lesions. Whole animal tests showed only a mild significant impairment of the forelimbs. Studies of the mechanical properties of selected isolated fast- and slow-twitch muscles demonstrated that slow-twitch muscles were significantly weaker in capn3(-/-) mice than in wild-type mice. Three different tests showed that there was no membrane disruption, suggesting a nonmechanical etiology of capn3(-/-) mice dystrophy. These findings are consistent with a mechanism involving signaling systems.
Fougerousse
Françoise
F
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8115-Généthon, 1 rue de l'Internationale, BP 60, 91002 Evry, France. fougerou@genethon.fr
Gonin
Patrick
P
Durand
Muriel
M
Richard
Isabelle
I
Raymackers
Jean-Marc
JM
D000818:Animals; D002154:Calpain / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D017097:Electric Impedance; D005260:Female; D051379:Mice; D008817:Mice, Mutant Strains; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010641:Phenotype
D009124:Muscle Proteins; D002154:Calpain; C491373:Capn3 protein, mouse