Halothane resistance in Drosophila melanogaster: Development of a model and gene localization techniques

Studying genetically altered animals that are resistant to inhaled anesthetics may ultimately lead to an understanding of anesthetics' mechanism(s) of action. We studied the genetics of halothane resistance in a strain of Drosophila melanogaster that showed substantially increased resistance to halothane anesthesia. We developed a test method that allowed us to repeatedly observe several samples of flies exposed to the same concentration of halothane, and we measured halothane resistance. The 50% effective dose (ED(50)) of 91R flies (our resistant population) was greater than the ED(50) of Canton-S (our control strain) by 69% in females and by 48% in males. By assessing the contributions of the three major chromosomes of Drosophila to resistance, this study found that the X and third chromosomes of 91R have no effect on resistance, while the second chromosome has a major impact. Resistance within the second chromosome was further localized by testing marked recombinant chromosomes. The central region of 91R's second chromosome, bounded by the genes for black thoracic color and cinnabar eye color, determined most if not all of the increase in resistance. We were not able to further localize resistance within this segment of the second chromosome (containing about 8% of the total genetic map distance). An autosomal dominant gene for halothane resistance in 91R was localized to a small region of the second chromosome.