Mutation in the delta-subunit of the nAChR suppresses the muscle defects caused by lack of Dystrophin.
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.
Etard
Christelle
C
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch Cedex, CU de Strasbourg, France.
Behra
Martine
M
Ertzer
Raymond
R
Fischer
Nadine
N
Jesuthasan
Suresh
S
Blader
Patrick
P
Geisler
Robert
R
Strähle
Uwe
U
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D016189:Dystrophin / Q000172:deficiency*; D005455:Fluorescent Antibody Technique; D005775:Gastrula / Q000166:cytology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009068:Movement / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D016189:Dystrophin; D011978:Receptors, Nicotinic; D029961:Zebrafish Proteins; C511367:chrnd protein, zebrafish