Reverse genetics in Drosophila

Drosophila has been a genetic model system for nearly a hundred years. It offers easy rearing and genetic manupilation that has been outstandingly succesful in identifying functions of genes in animal Development and Disease. Classical genetic screens (so-called forward genetics) combine random mutagenesis with a phenotypic selection to identify genes important for biological processes. However this approach is laborious and may not identify all relevant genes. Since spring 2001 the Drosophila genomic sequence has been available. This offers an invaluable tool to study gene function in biological processes. Ideally one would like to reduce or delete a genes function at will (so-called reverse genetics). Last year a targeted gene knockout techniquee was described in Drosophila (Rong and Golic, 2001. & Rong, 2002)This approach is still laborious and has still to prove its general usefulness. Double stranded RNA interference (RNAi) can reduce gene expression in a sequence-specific manner in diverse organisms by targeting homologous mRNA for degradation (reviewed in Hammond et al., 2001). Recently a modified double stranded RNA interference (RNAi) technique was described to be able to selectively reduce gene function to a level comparable to loss of gene function in several genes (Kalidas and Smith, 2002). This technique allows double stranded RNA molecules to be made following splicing out of intron sequences in the tandem inverted coding DNA. The geniality of this technique is that it lends itself to expression in many tissues and cell types at a chosen timepoint in a flies life, be it egg, embryo,larvae or adult flies due to the numerous genetic tricks available in Drosophila for gene expression. This technique holds great promise for a systematic search for gene function in the biological process of choice. To read about RNAi as high through-put screens visit the web page of Cenix Gmbh.