Abstract
This chapter discusses several Drosophila models of polyglutamine disorders. Drosophila models are sensitized genetic systems that permit the power of fly genetics to be harnessed in an effort to identify modifier genes or compounds. The first Drosophila model of polyglutamine disorder expressed a truncated form of ataxin-3/MJD, the mutant protein in Spinocerebellar ataxia type 3 (Machado-Joseph disease, MJD). The second fly model of polyglutamine disease to appear used amino-terminal fragments of huntingtin cDNA encoding 75 or 120 glutamine residues. This fragment includes exons 2, 3, and a portion of 4. By using the numbering system of the published IT15 sequence encoding 23 repeats, these constructs encode the first 171 amino acids of human huntingtin. Another fly model of SCA1 reported the results of P element screen for modifiers. These fly models have shown their worth in the validation of small compounds predicted to inhibit polyglutamine pathogenesis on the basis of cell-based researches. © 2006 Elsevier Inc. All rights reserved.