Profiling for genetic interactions with mutant Idh in vivo. (A) Genetic modifiers that enhanced the melanotic mass phenotype induced by mutant Idh were identified by crossing stocks containing a genetic modifier with hml-Gal4, UAS-2xEGFP; UAS-Idh-R195H homozygotes. The resulting offspring were heterozygous for hml-Gal4, UAS-Idh-R195H, and the genetic modifier. Crosses were carried out at 31°C to enhance the melanotic mass phenotype. Penetrance of melanotic masses is shown for 91 crosses in order of increasing penetrance of the melanotic mass phenotype in the F1 flies. (B) Genetic modifiers that suppressed or enhanced the mutant Idh–induced wing phenotype were identified by crossing stocks containing a genetic modifier with CCAP-Gal4, UAS-Idh-R195H homozygotes at 25°C. The resulting offspring were heterozygous for CCAP-Gal4, UAS-Idh-R195H, and the genetic modifier. Penetrance of the wing-expansion defect in 107 crosses is shown in order of increasing penetrance of the wing phenotype. Note the log scale on the y-axis to show the range of phenotype penetrance, with strong suppressors almost completely rescuing the phenotype, and strong enhancers producing almost complete penetrance. (C) Crosses with stocks modifying catalase (CAT) and SOD2. Introduction of SOD2, CAT, or double-stranded RNA targeting CAT to CCAP neurons expressing Idh-R195H. SOD2, superoxide disumutase 2.