The influence of up-regulating basket in a Drosophila model of Machado-Joseph Disease. Catherine Romberger, John Warrick. University of Richmond, Department of Biology, Richmond, VA.

   Machado-Joseph Disease/ Spinocerebellar Ataxia 3 (MJD/SCA3) is a dominantly inherited, neurodegenerative disease caused by an expansion of a naturally occurring glutamine repeat in the coding region of the Ataxin-3 (ATX3) protein. The mutant expanded glutamine ATX3 formes aggregates within the nucleus of cells. These aggregates are thought to impede cellular function and lead to toxicity. The basket (bsk) gene is the homologue of the human c-Jun N-terminal kinase (JNK), which is involved in autophagy and, when stimulated by stress, removes old proteins from the cell. Research suggests that JNK has a role in other neurodegenerative diseases including Huntingtons disease, which is in the same family of diseases as MJD. We hypothesized that the up-regulation of the bsk pathway may increase the removal of these aggregates, decreasing the severity of neurodegeneration. In order to test this hypothesis, UAS-ATX 3 alleles of mutant and normal MJD as well as UAS-BSK were expressed in the fly eye using a Gal4 driver. In order to determine the level of degeneration, fly heads were fixed and embedded in epon blocks and semi-thin sections of retinas were evaluated using light microscopy. In order to determine the amount of aggregates present, flies were aged and frozen sections were stained with antibodies to ATX3. The sections were viewed using confocal fluorescence microscopy. Our results suggest that the co expression of bsk influences the amount of degeneration of the photoreceptors and the number of aggregates.