unc-58 was first identified by dominant mutations that cause hypercontracted body-wall and egg-laying muscle in C. elegans.
unc-58(dm) animals are rigidly paralyzed and egg-laying constitutive. Putative loss-of-function
unc-58 alleles have been isolated as revertants of the
unc-58(dm) phenotype. These alleles have no obvious phenotype on their own, suggesting that
unc-58(dm) mutants result in an inappropriately activated gene product.
unc-58(dm) stands out among other muscle activation mutations because it has the following unusual phenotypes. First,
unc-58(dm) animals frequently flip around their longitudinal axis. This phenotype is, to our knowledge, not found in any other C. elegans mutant. Second, the
unc-58(dm) phenotype is partially rescued by the drug endosulfan, an antagonist of GABA-gated chloride channels (B. Wightman and G. Garriga, personal communication; our unpublished data). Third,
unc-58(dm) alleles exhibit a defect in the outgrowth of HSN neuron projections (B. Wightman and G. Garriga, personal communication). We plan to clone the
unc-58 gene and perform further genetic, pharmacological and molecular experiments to elucidate its mechanism and site of function.
unc-58 has been mapped to a region between
unc-115 and
dpy-6 on the X chromosome (D. Thierry-Mieg, personal communication). We have obtained putative Tc1 insertions in
unc-58 by screening in a
mut-6 background for revertants of the uncoordinated phenotype of an
unc-58(dm) allele. We will use cosmids that cover the
unc-58 region as probes to identify the Tc1 insertions. Because the
unc-58(dm) mutation affects muscle excitability, it may encode an ion channel or a regulator of ion channel activity.