Worm Breeder's Gazette 3(1): 15

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.

More on Levamisole-resistant Mutants

J. Lewis

For those of you who remember my eclectic spiel at the April worm 
meeting, Gideon Goldstein's thymopoietin and a low molecular weight 
peptide derivative turn out to have no cholinergic effect on C.  
elegans.  However, levamisole itself appears to be an excellent 
molecule from which to produce an affinity reagent.  In confirmation 
of the work of American Cyanamid and Janssen Pharmaceutica on 
parasitic nematodes, we have tested substituted levamisole derivatives 
on C.  elegans and find that even bulky substituents (3-
chlorobenzamido) at the meta position of the phenyl ring have little 
effect on the activity of levamisole.  Suitable biochemical and 
histochemical affinity reagents can probably be made by coupling meta-
amino-levamisole via a spacer to an enzyme or an iodinated protein 
molecule.
A striking difference in motor behavior exists between L1 larvae and 
adults for all levamisole-resistant unc loci.  Mutant adults generate 
a decayed sine wave moving in the forward direction but move backward 
quite well.  Newly hatched L1 mutant larvae move forward only very 
spastically and backward not at all.  The ability to move forward 
graduates into that of the mutant adult throughout the L1 stage.  At 
about 22 hours after hatching at 20 C (mid to late L2) the ability to 
move backward is rapidly gained by uncs of all seven uncoordinated 
resistance loci.  The switch might indicate the on-point for a new 
pathway in the developing ventral cord.  Our notions are paradoxical 
to the ideas that the driving motorneurons (AS,A,B) of the ventral 
cord are entirely cholinergic and that the motorneurons of the cord 
function in a symmetric fashion with respect to forward and backward 
motion.  Of several other neurotransmitters tried in our cut-worm 
assay on the wild type C.  elegans, GABA is the only one found with a 
clear-cut effect, producing the flaccid paralysis previously described 
by Sulston and others (more might be said about this some other time).
We have found some differences in Triton X-100 extractable proteins 
amongst the wild type and two of our levamisole-resistant uncs but it 
remains to be proven the differences are related to levamisole 
resistance.