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, Differentiation culture medium (DM): DMEM, 2% horse serum and antibiotics (50 units.mL À1 penicillin and 50 ?g. mL À1 streptomycin)

, Cell culture incubator, vol.37, issue.2

, C2C12 cells seeded at 2.10 4 cells/cm 2 in 12-well plate for real time quantitative PCR (RT-qPCR) and immunostaining experiment

, HiPerfect ® transfection reagent

, Standard culture growth medium (GM): DMEM, 10% fetal bovine serum, and antibiotics (50 units.mL À1 penicillin and 50 ?g.mL À1 streptomycin)

, Differentiation culture medium (DM): DMEM, 2% Horse serum and antibiotics (50 units.mL À1 penicillin and 50 ?g. mL À1 streptomycin)

. Paraformaldehyde-4%-in and . Pbs,

, Permeabilization solution: 20 mM HEPES, 300 mM sucrose, 50 mM NaCl, 3 Mm MgCl 2 , 0.5% Triton X-100

, Blocking buffer: PBS, 10% goat serum, 1% bovine serum albumin (BSA), 0.1% Triton X-100

, Washing solution 1: PBS, 0.2% BSA

, Primary antibody: monoclonal anti-myosin skeletal fast, clone My-32, mouse antibody (anti-MyHC, Sigma Aldrich) 1:400 diluted in PBS-1% BSA solution

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:. Mots, . Gasp, and . Myostatine, Both lines Tg (Gasp-1) and Tg(Gasp-2) exhibit an increase in muscle mass due to myofiber hypertrophy without hyperplasia. However, Tg(Gasp-1) mice have an overall deregulation of glucose homeostasis and metabolic defects with age, a phenotype not found in Tg(Gasp-2) mice. These results allowed us to propose the GASP-2 protein as a better therapeutic candidate for muscle diseases. In the skeletal context, only the Gasp-2 overexpression leads to a bone phenotype. Altogether, our findings highlighted a gene expression regulatory network of TGF-ß members and their inhibitors in muscle. RESUME GASP-1 et GASP-2 sont deux protéines très proches structuralement caractérisées par plusieurs modules inhibiteurs de protéases et identifiés comme des inhibiteurs de plusieurs membres de la famille TGF-ß tel que la myostatine ou GDF-11, respectivement régulateurs négatifs de la myogenèse et de l'ostéogénèse. Malgré l'organisation structurale commune des protéines GASPs, leurs profils d'expression différents laissent supposer des rôles physiologiques distincts. C'est pourquoi, nous avons généré des modèles souris Tg(Gasp-1) et Tg(Gasp-2) surexprimant Gasp-1 ou Gasp-2 afin de mieux appréhender les fonctions de ces protéines, souris ABSTRACT GASP-1 and GASP-2 are two closely related proteins structurally characterized by several protease inhibitor modules and identified as inhibitors of several members of the TGF-ß family such as myostatin or GDF-11, negative regulators of myogenesis and osteogenesis, respectively

:. Mots, . Gasp, A. Myostatine, and G. Gasp-1, are two closely related proteins structurally characterized by several protease inhibitor modules and identified as inhibitors of several members of the TGF-ß family such as myostatin or GDF-11, negative regulators of myogenesis and osteogenesis, respectively. Despite the common structural organization of GASPs proteins, their different expression profiles suggest distinct physiological roles. We generated Tg(Gasp-1) and Tg(Gasp-2) mouse models overexpressing Gasp-1 or Gasp-2 in order to better understand the functions of these proteins. Functional analyses, carried out in vitro and in vivo in muscular, skeletal and anti-proteasic context, allowed us to highlight a functional duality between GASP-1 and GASP-2 in the different contexts. Both lines Tg (Gasp-1) and Tg(Gasp-2) exhibit an increase in muscle mass due to myofiber hypertrophy without hyperplasia. However, Tg(Gasp-1) mice have an overall deregulation of glucose homeostasis and metabolic defects with age, a phenotype not found in Tg(Gasp-2) mice. These results allowed us to propose the GASP-2 protein as a better therapeutic candidate for muscle diseases