Nitric oxide synthase is not essential for Drosophila development

Nitric oxide (NO) is a key regulator of diverse biological processes, including the modulation of blood vessel tone [1]. Nitric oxide synthase (NOS), which oxidizes arginine to produce NO and citrulline [2], is found in organisms from bacteria to humans. Despite the impact of NO on physiology, mice lacking all three mammalian NOS isoforms develop to term and are viable [3]. There is a single NOS ortholog encoded in the Drosophila genome (Nos). Regulski et al. [4] described a mutation in a conserved residue that abrogates NOS activity, and reported that this lesion confers lethality (NosC). However, two lines of evidence led us to believe that this lethality could be due to a closely associated mutation rather than the lesion in Nos itself. First, the lethality was not rescued by reintroduction of NOS. Second, while the authors convincingly demonstrate that they have generated a mutation in the Nos gene that inactivates the enzyme, they do so for only one of the 17 alleles that they assign to the Nos complementation group. Beginning with a stock of NosC provided by Regulski et al. [4], we isolated recombinant chromosomes in which we separated the lethal lesion from the point mutation in NosC. Additionally, we generated a deletion that removes significant portions of the Nos coding sequences, including those responsible for synthesis of NO, and found it to be homozygous viable. Both our deletion and NosC eliminate NOS enzymatic activity without affecting Drosophila development, and without obviously compromising the health of the flies. We created a transgenic line carrying the Nos cDNA (Dijkers and O’Farrell, unpublished data). Its Correspondences