Résumé :
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In a previous study, we have identified the canonical Wnt signaling pathway as a putative target for inactivation of myostatin (MSTN) in mice. Here1 we have analysed the Mouse WNT signaling pathway in MSTN-null vs wild-type mice (n=5 animals/group) using a commercial qPCR array. The analysis revealed changes of expression for members of the "Frizzled-2-signaling pathway" as shown by up-regulation of Wnt4, Wnt2, and Wnt5b transcripts and down-regulation of Wnt11, Wnt16, WNT3A, Wnt2b, and Wnt5a transcripts. Similarly, changes in the expression of Wnt receptors and their co-receptors (up-regulation of FZD8, LRP5, and down-regulation of Fzd7, Fzd1, Fzd5, Fzd3, LRP6, Kremen1), regulators of proliferation (up-regulation of pp2ca, FGF4, Tcf7, and Wisp1; down-regulation of c-jun) and transcription factors (up-regulation Tcf7,and myc; down-regulation of Aes, T, Tle2, BCL9, and Tle1) were detected. The differential expression of some genes was validated by qPCR and transcriptomic data, e.g. Wnt16, Kremen 1, FRZB, SFRP2, AES, Wnt4, FZD8, and TCF7. Thus, our study showed differences in expression level of components beta-catenin-TCF, illustrating a complexity in the response, which remains to be elucidated. As the Wnt signaling pathway is crucial for maintaining the balance between proliferation and differentiation throughout development and postnatal life, these changes could account for muscle hypertrophy. Work is now in progress in models in which MSTN is increased (electrotransfert in mouse tibialis, transfection of C2C12 cell line). 1: MYOTROPHY, ANR BLAN08-2_309209, 2009-2011
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