Worm Breeder's Gazette 2(2): 36
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.
Mutants resistance to levamisole can occur at about 12 genetic loci in C. elegans. Excepting several anomalous mutants, all mutants fall into three classes determined by similarity in visible and pharmacological phenotypes: uncoordinated (6 loci); pseudo-wild type ( 4 loci); and twitcher (2 loci). Pharmacologically, the uncs are severely deficient in acetylcholine receptors and the pseudo-wild types modestly so. The defect in twitchers is downstream physiologically from the acetylcholine receptor and probably intramuscular. Twitchers and E190 (an unc-54, myosin-defective allele) have been shown to suppress a number of dumpy mutants, suggesting at least some dumpies are muscle hypercontraction mutants. The twelve loci have ben mapped. Five of the unc fall on LGI. Three very close loci were mapped at high resolution; two might be contiguous genes, a mutant locus unrelated to levamisole-resistance occurs between these and the third locus. Ts mutants and differences in drug susceptibility suggest that at least two of the commonly occurring unc loci code for structural peptides of the receptor. Genetic and pharmacological properties of some of the other loci hint involvement in developmental regulation or receptor processing. Particularly interesting are head-body differences which have also been noted by Johnson and Russell in their cholinesterase mutant and by Brenner and others in muscle mutants. It appears that levamisole is a nicotinic depolarizing blocking analog of acetylcholine, a fortuitous selective agent. The difficulty of obtaining clean-cut cholinergic mutants with cholinesterase inhibitors probably resides in nonspecific toxicity of these inhibitors (e.g. inhibition of digestive esterases). We surmise that although excessive stimulation with cholinergic agents is toxic to C. elegans, much of cholinergic physiology per se is unessential to the worm. The miniscule amounts of receptor present are a serious but not insurmountable obstacle to what would otherwise appear a very powerful system for studying eukaryotic gene regulation. The strong pharmacological resemblance of the nematode receptor to a vertebrate sympathetic nicotinic receptor might be useful for getting grant money.