title: Loss of selenoprotein N function causes disruption of muscle architecture in the zebrafish embryo.
abstract: Mutations in the gene coding for selenoprotein N (SelN), a selenium containing protein of unknown function, cause different forms of congenital muscular dystrophy in humans. These muscular diseases are characterized by early onset of hypotonia which predominantly affect in axial muscles. We used zebrafish as a model system to understand the function of SelN in muscle formation during embryogenesis. Zebrafish SelN is highly homologous to its human counterpart and amino acids corresponding to the mutated positions in human muscle diseases are conserved in the zebrafish protein. The sepn1 gene is highly expressed in the somites and notochord during early development. Inhibition of the sepn1 gene by injection of antisense morpholinos does not alter the fate of the muscular tissue, but causes muscle architecture disorganization and greatly reduced motility. Ultrastructural analysis of the myotomes reveals defects in muscle sarcomeric organization and in myofibers attachment, as well as altered myoseptum integrity. These studies demonstrate the important role of SelN for muscle organization during early development. Moreover, alteration of myofibrils architecture and tendon-like structure in embryo deficient for SelN function provide new insights into the pathological mechanism of SelN-related myopathy.
authors.affiliation: Institut de Biologie Moléculaire et Cellulaire, UPR ARN du CNRS/Université Louis Pasteur, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Marzanna
authors.initials: M
authors.lastname: Deniziak
authors.forename: Christine
authors.initials: C
authors.lastname: Thisse
authors.forename: Mathieu
authors.initials: M
authors.lastname: Rederstorff
authors.forename: Colette
authors.initials: C
authors.lastname: Hindelang
authors.forename: Bernard
authors.initials: B
authors.lastname: Thisse
authors.forename: Alain
authors.initials: A
authors.lastname: Lescure
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009132:Muscles / Q000196:embryology* / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051140:Selenoproteins / Q000172:deficiency* / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D051140:Selenoproteins; D029961:Zebrafish Proteins; D012313:RNA