Figure 1. Elevated rates of spontaneous and stress-induced loss-of-heterozygosity in Mnn1 RNAi and deletion mutants.

A loss-of-heterozygosity (LOH) assay based on mutations in the multiple wing hairs (mwh) gene was used to assess genomic instability in Mnn1 transgenic strains and deletion mutants. (A) A fly heterozygous for mwh has one wing hair per cell. (B) A fly homozygous for mwh has two or more hairs per cell. (C) LOH is elevated in Mnn1^e173 deletion mutant flies. Individual cells that have lost the wild-type mwh gene are observed within a field of heterozygous cells (arrows in C). Panels A & C show individuals that have received short, repeated heat shock treatments. (D&E) In the absence of stress, the incidence of mwh^- cells is increased significantly in Mnn1 deletion mutants (Mnn1^e30;mwh/+ and Mnn1^e173;mwh/+) and flies expressing the UAS construct for Mnn1 RNAi under the control of tubulin-GAL4 (Mnn1-RNAi/+; tub-GAL4/mwh) (p<0.05). These elevated rates of LOH are significantly enhanced by short (20 min), repeated heat shock treatments (D) and by short (1 hr), repeated hypoxia treatments (E). Mnn1/+; tub-GAL4/mwh refers to a strain harboring a UAS construct for menin over-expression; this strain does not show a significant difference in the frequency of LOH. The average number of mwh^- cells per wing is indicated. Error bars represent standard errors of the mean (SEM). Stars denote significant differences compared to wild-type controls (mwh/+) of the same condition, p<0.05.