Schema for Generation of Fly Models of Neurodegenerative Diseases

<p>A variety of driver lines are available that express the yeast transcriptional co-activator GAL4; shown is GMR-GAL4, which uses regulatory DNA that responds to the <i>glass</i> transcription factor to induce expression of GAL4 in all cells of the eye beginning in larvae (A). The cDNAs encoding human disease-associated genes, such as that for Atx3, which causes SCA3, are subcloned into the UAS expression construct (B) and used to generate transgenic flies. When these flies (B) are crossed with those of a driver line (A), GAL4 is expressed in the progeny and induces expression of the disease gene, producing an abnormal eye phenotype that can readily be scored under the dissection microscope. A stable tester stock can be established that expresses both of these transgenes and used to carry out genetic screens. In the case of the EP element (C), in the presence of GMR-GAL4 (A), genomic sequences near the EP element can be identified that modulate severity of the tester stock.