Résumé :
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Gasp-1 (Growth and differentiation factor associated serum protein 1) contains multiple domains associated with protease-inhibitory proteins. Like its homologous protein Gasp-2, Gasp-1 is able to bind both Gdf8 and Gdf11, two secreted factors that regulate skeletal muscle mass and on anterior/posterior paterning in the axial skeleton respectively. In vitro, Gasp-1 has been characterized as a Gdf8 inhibitor (Hill et al., 2003). The analysis of Gasp-1 and Gasp-2 expressions did not provide obvious clues on their biological function. However, Gasp-1 and Gasp-2 are both expressed in fetal skeletal muscle like Gdf8, suggesting that those proteins may have a critical role to play in skeletal muscle development by controlling the Gdf8 function. As part of a larger project focusing on the genetic determinism of muscular characteristics in cattle, we have undertaken functional analysis of Gasp-1 and Gasp-2 on mice. From Gasp-1 overexpression analysis in different myoblast cells lines, we show a significant increase of cell proliferation and differentiation. Besides, we have generated transgenic mouse lines overexpressing Gasp-1 (Surgasp-1) under the control of a CMV promoter. These mice showed a 35% increase of muscular mass, resulting from a combination of muscle cell hyperplasia as well as hypertrophy. Among 28 biochemical parameters, only the lactate level is affected in the Surgasp-1 mice. Although the Gasp-1 overexpression is observed in brain, heart, spleen, liver, lung and kidney, we haven't noticed significant effects on the development of these organs, suggesting that Gasp-1 could open prospects to treat muscular diseases and disorders, particularly those in which an increase in muscle tissue would be therapeutically beneficial.
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