The alterations that we observed in Lightweight heterozygotes in response to ethanol and anesthetics are qualitatively similar to what has been reported previously in C. elegans and Drosophila; however, important differences exist. In invertebrates, unc-79 mutants are very hypersensitive to halothane [10]; whereas, we observed no alterations in MAC for halothane in Lightweight heterozygotes. However, we did observe that Lightweight heterozgotes are resistant to isoflurane. It is unclear at this point why these species differences exist. One possibility is that most of the unc-79 alleles tested in invertebrates were true null mutations; whereas, we tested heterozygous mutant mice. Another possibility is that a truncated protein might be produced in Lightweight heterozygotes, which could interfere with the proper functioning of this pathway in unanticipated, even opposite, ways. It should be noted that the fact that Lightweight heterozygotes were resistant to isoflurane and not to all anesthetic agents tested suggests that the anesthetic phenotype does not simply reflect a non-specific alteration in neuronal function.
