Résumé :
|
We aim at characterizing muscle function in a cohort of different animal models for LGMD2 using mechanical parameters in several isolated muscles. Non invasive techniques will also be applied such as grip, escape or wire tests and measurements of muscular force coupled to magnetic resonance imaging and spectroscopy. The ultimate purpose of the project is to follow the effects of therapies in these models. Alpha-sarcoglycanopathy (LGMD2D) is an autosomal recessively inherited limb-girdle muscular dystrophy caused by mutations in the alpha-sarcoglycan gene, SGCA. Disruption of the SGCA gene in mouse (sgca-null) recapitulates many of the clinical phenotypes observed in patients. These mice developed progressive muscular dystrophy. We first measured the significant decrease of force of the isolated muscles in 2 to 6 month-old sgca-null mice. The most dramatic difference with the wild-type mice was observed after a series of eccentric contractions (the loss of force being more than 40% in 2.5 monthold mice). Considering the severity of the sgca-null mice, we used this model for setting up different assays to get a longitudinal study. Global activity of the animals evaluating the pulling force or the forelimb muscle strength or endurance by different classical means illustrated their weakness. Other experiments of animals of 4 and 6 month-old were able to detect an impressive decrease of force after repeated electrical stimulation coupled to magnetic resonance imaging and spectroscopy. These animals did not show any difference in their energy metabolism compared to the control mice. This approach will help to evaluate the efficiency of pharmaceutical or gene therapies and define parameters that will be worth to study during clinical trial in human.
|