In order to identify the molecular mechanisms underlying acute functional tolerance (AFT) to ethanol, we performed an unbiased genetic screen for animals that are impaired in the ability to develop AFT. We have previously shown that NPR-1 activity antagonizes the development of AFT; in an npr-1 mutant background, AFT develops more quickly than in wild type, suggesting that NPR-1 function acts to slow the development of AFT [4]. We took advantage of this phenotype of fast and obvious development of AFT in the npr-1 mutant background to sensitize our screen to make it easy to identify animals with diminished AFT. The advantage of using this sensitized background is that we should be able to identify mutations in which AFT is diminished but not completely abolished, which would be difficult in the N2 wild-type background.
