title: Increased muscle stress-sensitivity induced by selenoprotein N inactivation in mouse: a mammalian model for SEPN1-related myopathy.
abstract: Selenium is an essential trace element and selenoprotein N (SelN) was the first selenium-containing protein shown to be directly involved in human inherited diseases. Mutations in the SEPN1 gene, encoding SelN, cause a group of muscular disorders characterized by predominant affection of axial muscles. SelN has been shown to participate in calcium and redox homeostasis, but its pathophysiological role in skeletal muscle remains largely unknown. To address SelN function in vivo, we generated a Sepn1-null mouse model by gene targeting. The Sepn1(-/-) mice had normal growth and lifespan, and were macroscopically indistinguishable from wild-type littermates. Only minor defects were observed in muscle morphology and contractile properties in SelN-deficient mice in basal conditions. However, when subjected to challenging physical exercise and stress conditions (forced swimming test), Sepn1(-/-) mice developed an obvious phenotype, characterized by limited motility and body rigidity during the swimming session, as well as a progressive curvature of the spine and predominant alteration of paravertebral muscles. This induced phenotype recapitulates the distribution of muscle involvement in patients with SEPN1-Related Myopathy, hence positioning this new animal model as a valuable tool to dissect the role of SelN in muscle function and to characterize the pathophysiological process.
authors.affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Rederstorff
authors.forename: Perrine
authors.initials: P
authors.lastname: Castets
authors.forename: Sandrine
authors.initials: S
authors.lastname: Arbogast
authors.forename: Jeanne
authors.initials: J
authors.lastname: Lainé
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vassilopoulos
authors.forename: Maud
authors.initials: M
authors.lastname: Beuvin
authors.forename: Odile
authors.initials: O
authors.lastname: Dubourg
authors.forename: Alban
authors.initials: A
authors.lastname: Vignaud
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ferry
authors.forename: Alain
authors.initials: A
authors.lastname: Krol
authors.forename: Valérie
authors.initials: V
authors.lastname: Allamand
authors.forename: Pascale
authors.initials: P
authors.lastname: Guicheney
authors.forename: Ana
authors.initials: A
authors.lastname: Ferreiro
authors.forename: Alain
authors.initials: A
authors.lastname: Lescure
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015151:Immunoblotting; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009043:Motor Activity; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology*; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D010641:Phenotype; D050050:Protein Carbonylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology / Q000523:psychology; D013550:Swimming / Q000523:psychology
chemical_list: D009124:Muscle Proteins; C545253:SEPN1 protein, mouse; D051140:Selenoproteins