Résumé :
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SEPN1-related myopathy is a rare disorder characterized by axial muscle weakness, scoliosis and respiratory failure, and caused by mutations in the SEPN1 gene, encoding selenoprotein N (SelN). This entity gathers four autosomal recessive muscular pathologies with molecular, clinical and morphological overlap: Rigid Spine Muscular Dystrophy, the classical form of Multi-minicore Disease, rare cases of Desmin-Related Myopathy with Mallory Body-like Inclusions and Congenital Fibre Type Disproportion. SelN is a glycoprotein of as yet unknown function, localized in the membrane of the endoplasmic reticulum. As all selenoproteins, SelN is characterized by a specific selenocysteine residue in its peptidic sequence. The clinical features observed in patients and the defects in muscle organization seen in zebrafish mutants, led us to hypothesize that SelN may play a role during muscle development and/or maintenance. To precise Sepn1 expression during murine development and due to a lack of robust antibodies against SelN, we used RNAbased approaches: quantitative RT-PCR (qRT-PCR), performed on cDNA obtained from isolated adult and embryonic tissues, and whole mount in situ hybridization. We demonstrated that Sepn1 is expressed early during embryogenesis, with a strong expression already detected at E9. By qRT-PCR, we showed that this expression increases until E12 and then markedly decreases. Between E15 and E18, its decline is also detected in most isolated tissues. After birth, a strong reduction is observed with age in most tissues, leading to barely detectable levels at 6 weeks. In some rare tissues, such as liver, Sepn1 expression was not detectable, neither in embryos nor after birth. These results indicate that SelN is developmentally regulated in mice and correlate with data obtained in human that showed it is strongly down regulated during myoblasts differentiation. We are currently investigating muscle embryonic development in SelN deficient mice by characterizing the expression of myogenic factors in Sepn1-/- embryos.
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