Genetic modification tools in mosquitoes revolutionize our ability to functionally analyze insecticide resistance

Mosquito transmitted diseases are of global importance causing morbidity and mortality worldwide. The main way to prevent these diseases is through vector control. Insecticide-based vector control interventions have had impres-sive results, but are now threatened by the rising levels of insecticide resistance in mosquito populations. Molecular and biochemical research has revealed several mechanisms associated with the phenotype of insecticide resistance, which is an important first step for designing mitigation strategies. Functional validation of the mechanisms has been achieved in some cases, however, the role (if any) of many candidate genes and genetic modifications remains elusive. We also lack critical knowledge on the effect size of each mechanism and how the different mechanisms interact to determine the intensity of the phenotype. In this review we focus on the available genetic modification tools in mosquitoes and how their use can help us better understand the mechanisms of insecticide resistance. We also present studies where these tools have been used to validate the role of detoxification enzymes and target site mutations and discuss the advantages and limitations of this approach compared to other available methodologies.