Worm Breeder's Gazette 2(1): 18
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
As described by Brenner, a large fraction of levamisole-resistant mutants are worms with a wild type visible phenotype when grown on NG plates. We find that most of these mutants grown in the presence of levamisole acquire the peculiar uncoordinated phenotype characteristic of the levamisole-resistant uncs. In our cut worm assay, several of these 'wild type' mutant strains showed near wild type susceptibility to all drugs tested (including levamisole) when grown in the absence of levamisole. Grown and tested in the presence of levamisole, the worms showed extreme resistance to cholinergic agonists but sensitivity to the muscle contracting agent ouabain. The latter pharmacological phenotype is characteristic of levamisole-resistant uncs and N2 wild type worms treated with cholinergic blocking agents. As we mentioned previously, levamisole also acts as an agonist on naive worms and is blocked by cholinergic antagonists. From these observations, we infer that levamisole is a cholinergic depolarizing blocking agent. We believe that mutants with a normal visible phenotype have less of and/or less functional acetylcholine receptors than the wild type-but still workable receptors. Possibly, levamisole depolarizes in binding to the Ac receptor but once bound, has a blocking effect. N2 wild type worms grown on levamisole would always have a significant amount of muscle-depolarization due to constant dissociation and reassociation of levamisole with the receptor, whereas the wild type mutants would have an insignificant absolute amount of receptor undergoing this flux-hence only the blocking effect is seen after recovery from initial exposure to the drug. By far the largest fraction and the most resistant 'wild type' mutants fall into a gene probably corresponding to tmr-1 described by Brenner. Very rare mutants in this gene are levamisole-resistant uncs when homozygous and semi-dominant in the growth test on levamisole! Most of the other wild type mutants appear to be leaky alleles of the levamisole-resistant unc loci. A couple of rare birds are sex-linked and apparently sexually dimorphic. Four rather different mutants have been isolated with close to wild type visible phenotype and extreme resistance to levamisole even when grown in the absence of the drug. In the cut worm assay they show extreme resistance to levamisole and varying susceptibility to other cholinergic agonists (unfortunately not a wild type susceptibility to acetylcholine). These might be mutants having the minimal amount of functional Ac receptor necessary for a wild type visible phenotype; we prefer to think that they are acetylcholine binding protein mutants. Three of the four mutants are in unc-29, LG I.