The RU486-dependent activation of the GeneSwitch system in adult muscles leads to severe adverse effects in Drosophila

Abstract

Robust genetic systems to control the expression of transgenes in a spatial and temporal manner are a valuable asset for researchers. The GeneSwitch system induced by the drug RU486 has gained widespread use in the Drosophila community. However, some concerns were raised as negative effects were seen depending on the stock, transgene, stage and tissue under study. Here, we characterized the adverse effects triggered by activating the GeneSwitch system in adult muscles using the MHC-GS-GAL4 driver. When a control, mock UAS-RNAi transgene was induced by feeding adult flies with RU486, we found that the overall muscle structure, including myofibrils and mitochondrial shape, was significantly disrupted and led to a significant reduction in the lifespan. Remarkably, lifespan was even shorter when two copies of the driver were used even without the mock UAS-RNAi transgene. Thus, researchers should be cautious when interpreting the results given the adverse effects we found when inducing RU486-dependent MHC-GS-GAL4 in adult muscles. To counter the impact of these effects we recommend setting up additional control groups, such as a mock UAS-RNAi transgene, to validate the findings when using this inducible genetic system, as comparing the phenotypes between RU486-treated and untreated animals could be insufficient.