Résumé :
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Introduction : Spinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by the degeneration of the alpha-motor neurons in the spinal cord. The loss of these neurons causes proximal, symmetrical limb and trunk muscle weakness that progresses to paralysis and ultimately to death. To get a better understanding of the various steps in the pathogenesis of SMA, different knock out and transgenic approaches have been employed to generate suitable mouse models. These mouse models resemble the more severe type of human SMA, but it would be beneficial to generate mice with intermediate and mild phenotypes. Objective : To generate a hypomorphic allelic series of Smn knockdown in muscle and neuronal cell lines as well as in transgenic mice. Methods : In the present study, we have used the short interference RNA (siRNA) approach to selectively reduce Smn expression in cell culture and transgenic mice. Stable cell lines have been obtained and characterized at the protein and cell biological levels. Effect of Smn knockdown on cell growth properties, and on differentiation has been assessed. The transgenic mice are being characterized at a number of levels, including neuronal development.
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