PUBLICATION

Loss of selenoprotein N function causes disruption of muscle architecture in the zebrafish embryo

Authors
Deniziak, M., Thisse, C., Rederstorff, M., Hindelang, C., Thisse, B., and Lescure, A.
ID
ZDB-PUB-061205-15
Date
2007
Source
Experimental cell research   313(1): 156-167 (Journal)
Registered Authors
Lescure, Alain, Thisse, Bernard, Thisse, Christine
Keywords
Selenoprotein N, Selenocysteine, Congenital muscular dystrophy, Zebrafish, Muscle, Myoseptum
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • DNA, Complementary/genetics
  • Gene Expression
  • Humans
  • Molecular Sequence Data
  • Muscles/embryology*
  • Muscles/metabolism*
  • Nucleic Acid Conformation
  • RNA/chemistry
  • RNA/genetics
  • Selenoproteins/deficiency*
  • Selenoproteins/genetics
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/deficiency*
  • Zebrafish Proteins/genetics
PubMed
17123513 Full text @ Exp. Cell Res.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping