Mutation in the delta-subunit of the nAChR suppresses the muscle defects caused by lack of Dystrophin

Etard, C., Behra, M., Ertzer, R., Fischer, N., Jesuthasan, S., Blader, P., Geisler, R., and Strähle, U.
Developmental Dynamics : an official publication of the American Association of Anatomists   234(4): 1016-1025 (Journal)
Registered Authors
Behra, Martine, Blader, Patrick, Ertzer, Raymond, Etard, Christelle, Fischer, Nadine, Geisler, Robert, Jesuthasan, Suresh
acetylcholine receptor, delta subunit, myopathy, dystrophin, dystroglycan
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Cloning, Molecular
  • DNA Primers
  • Dystrophin/deficiency*
  • Fluorescent Antibody Technique
  • Gastrula/cytology
  • Immunohistochemistry
  • In Situ Hybridization
  • Movement/physiology*
  • Muscle, Skeletal/metabolism*
  • Muscle, Skeletal/pathology
  • Mutation, Missense/genetics*
  • Receptors, Nicotinic/genetics*
  • Receptors, Nicotinic/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
16245342 Full text @ Dev. Dyn.
Normal motility of the zebrafish embryo requires a large number of gene loci, many of which have human orthologues implicated in myasthenias and other myopathies. We have identified a mutation in the zebrafish that abolishes body motility. Embryos have narrower myofibrils and lack clusters of nicotinic acetylcholine receptors (nAChRs) on the surface of the somitic muscle. We mapped the mutation to the delta-subunit of the nAChR, showing this mutant to be a new allele of the previously named sofa potato (sop). The mutant allele carries a missense mutation in the extracellular domain altering the cysteine at position 150 to an arginine. The delta-subunit is expressed in all striated muscles in embryonic and early larval stages together with the alpha1, beta1, epsilon, and gamma-subunits of nAChR. In contrast to mammals that show switching from the gamma embryonic to the adult epsilon-subunit, the two subunits are coexpressed in zebrafish embryos. We, furthermore, demonstrated that the sop/delta-nAChR mutation is a suppressor of the myopathy caused by lack of Dystrophin. The myofiber detachment phenotype of Dystroglycan-deficient embryos was not suppressed, suggesting that Dystrophin and Dystroglycan play distinct roles in muscle formation and maintenance of muscle integrity. Developmental Dynamics, 2005. (c) 2005 Wiley-Liss, Inc.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes