The molecular mechanism(s) by which DEET (N,N-diethyl-m-toluamide) acts as an insect "repellent" has not been resolved. Using forward genetic screens in Caenorhabditis elegans, we have isolated five DEET-resistant mutants (
der-1) after EMS mutagenesis of DEET-sensitive N2. Two are allelic and have been mapped between 2.4 mu and 2.9 mu on linkage group (LG) IV. Specifically, 3F (factor) cross data between two markers
unc-5 (1.78 mu) and
egl-19 (3.34 mu) on LGIV showed that 11/22 (50%) Egl-19 recombinants were DEET-resistant and 11/22 (50%) were DEET sensitive for allele
hf175. In case of allele
hf176, the data were 19/32 (59%) and 13/32 (41%), respectively. In addition, all Lin-33 recombinants from the 3F cross between two references
unc-5 (1.78 mu) and
lin-33 (2.55 mu) showed DEET sensitivity in both
hf175 and
hf176. Several additional 3F crosses are in various stages of completion. Interestingly, wild-type strains CB4856, AB1, and AB2 have been shown to be DEET resistant relative to the wild-type strains N2 and CB4852, which are both DEET sensitive. These findings suggest that DEET-resistance may be more common than we originally expected. Successful cloning of the
der-1 gene is an important step not only to elucidate the mechanism of DEET action but may prove useful in designing the next generation of chemicals that helps reducing insect-borne-diseases.