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Le collagène XXII dans la formation et la fonctionnalité de la jonction myotendineuse chez le poisson zèbre, de l’embryon à l’âge adulte

Abstract : The myotendinous junction (MTJ) is a specialized extracellular matrix which allows the transmission of skeletal muscle forces to bones. My thesis project aimed at characterizing the in vivo role of COLXXII using the zebrafish as a model. The zebrafish col22a1 gene encodes COLXXII whose expression begins in the entire somite, and is then restricted gradually at the MTJ, where the protein is deposited. Morphants (Knockdown) develop a dystrophic phenotype and we have demonstrated that COLXXII is likely a member of the integrin a7ß1 anchoring complex. However, because morpholinos are efficient only few days after injection, our study was limited to early stages of zebrafish development. We thus generated two mutant lines (CRISPR-Cas9) invalidated for col22a1. The typical sarcolemmal interdigitations of the MTJ are almost absent in mutants, from larvae to adult (as in morphants), which could impact the force transmission and/or the muscle attachment to myosepta (tendons). In the two mutant lines, the same proportion of larvae displays a severe phenotype leading to fish death 14 days post-fertilization. On the contrary, other larvae survive without any obvious general phenotype. A first candidate genes approach was realized by qPCR and tends to show that the phenotypic differences may be due to both, variable expressivity and genetic compensation. Finally, I have shown that 6 months col22a1-/- fish show a highly decreased swimming capacity and consume more O2 during effort compared to wild type animals. Thus, we conclude that the musculoskeletal system efficiency seems altered in absence of COLXXII. Our results should allow considering COL22A1 as a candidate gene for muscular dystrophies with unclarified genetic cause.
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Submitted on : Tuesday, June 16, 2020 - 1:01:57 AM
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Marilyne Malbouyres. Le collagène XXII dans la formation et la fonctionnalité de la jonction myotendineuse chez le poisson zèbre, de l’embryon à l’âge adulte. Biologie animale. Université de Lyon, 2018. Français. ⟨NNT : 2018LYSE1224⟩. ⟨tel-02869390⟩

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