The Drosophila tyramine beta-hydroxylase gene is required for ethanol tolerance

Tyramine beta-hydroxylase (Tbh) is required for octopamine synthesis. To better understand the function of Tbh in neurotransmitter synthesis in Drosophila melanogaster, we analyzed the molecular genetic organization of the Tbh gene and found that it encodes multiple transcripts. The transcripts differed in their 5′ untranslated region, and the resulting proteins differed in size. We identified new Tbh alleles and generated a new D. melanogaster Tbh mutant, TbhDel3, using FLP/FRT recombination mutagenesis to remove the translational start site that was still present in TbhnM18 mutants. The TbhDel3 mutants shared ethanol tolerance and larval locomotion defects with the TbhnM18 mutants. However, they differed in their cellular stress response. While TbhnM18 mutants exhibited increased ethanol resistance following heat shock, the TbhDel3 mutant did not achieve a similar level of resistance. To develop normal levels of ethanol tolerance, Tbh is required in a subset of neurons in the adult brain, which was identified with a newly generated Tbh-Gal4 driver. Both Tbh overexpression and reduction resulted in reduced tolerance, suggesting that Tbh levels need to be tightly controlled. These results improve our understanding of neurotransmitter synthesis and Tbh-dependent behavior.