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.

Nematode Mutants Lacking Functional Acetylcholine Receptors

J.A. Lewis, C.-H. Wu, J. Levine, H. Berg

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.