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Mutation in the δ‐subunit of the nAChR suppresses the muscle defects caused by lack of Dystrophin
Author(s) -
Etard Christelle,
Behra Martine,
Ertzer Raymond,
Fischer Nadine,
Jesuthasan Suresh,
Blader Patrick,
Geisler Robert,
Strähle Uwe
Publication year - 2005
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20592
Subject(s) - biology , dystrophin , dystroglycan , zebrafish , utrophin , microbiology and biotechnology , protein subunit , mutant , mutation , genetics , muscular dystrophy , gene , laminin , extracellular matrix
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 δ‐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 δ‐subunit is expressed in all striated muscles in embryonic and early larval stages together with the α 1 , β 1 , ϵ, and γ‐subunits of nAChR. In contrast to mammals that show switching from the γ embryonic to the adult ϵ‐subunit, the two subunits are coexpressed in zebrafish embryos. We, furthermore, demonstrated that the sop/δ‐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 234:1016–1025, 2005. © 2005 Wiley‐Liss, Inc.