The vestigial locus of Drosophila melanogaster is involved in resistance to inhibitors of dTMP synthesis.
The vestigal (vg) gene encodes a nuclear protein which plays a major role in the formation of the wing of Drosophila. Resistance or sensitivity to aminopterin, an inhibitor of the dihydrofolate reductase enzyme in D. melanogaster, seems to be associated with a specific alteration in vg gene function. Wild-type and vg mutant strains selected for growth on increasing concentrations of aminopterin display changes in physiological and biochemical parameters such as viability on normal and aminopterin-containing media, duration of development, wing phenotype, dihydrofolate reductase activity, and cross-resistance to fluorodeoxyuridine (FUdR) and to methotrexate. Our results indicate that the mechanisms of resistance differ in the wild-type and mutant strains. The vg83b27 mutant, in which the major part of intron 2 of the vg gene is deleted, is associated with a high rate of resistance to FUdR, an inhibitor of thymidylate synthetase. Moreover, vg83b27/vgBG heterozygotes, which are wild type when grown on normal medium, display a strong vg phenotype when grown on aminopterin. Our results indicate a role for the vestigial locus in mediating resistance to inhibitors of dTMP synthesis.
Silber
J
J
Laboratoire de Genétique Quantitative et Moléculaire, Institut J. Monod (Université Paris 7), France.
Le Menn
A
A
Chevillard
S
S
Zider
A
A
Paumard
S
S
D000630:Aminopterin / Q000494:pharmacology; D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005467:Floxuridine / Q000494:pharmacology; D005493:Folic Acid Antagonists; D006579:Heterozygote; D008727:Methotrexate / Q000494:pharmacology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D013045:Species Specificity; D013938:Thymidine Monophosphate / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014921:Wings, Animal
D005493:Folic Acid Antagonists; D009687:Nuclear Proteins; D005467:Floxuridine; D013938:Thymidine Monophosphate; D000630:Aminopterin; D008727:Methotrexate