Caenorhabditis elegans as a Model System for Triplet Repeat Diseases

Common features underlie the generation and function of neurons in multicellular animals. It is likely that conserved pathways and genes also are involved in neuronal degeneration and malfunction. To address the molecular mechanisms of complex human neurological disorders, many investigators are choosing to study these diseases in simpler organisms. The nematode Caenorhabditis elegans provides an excellent model system to address genetically the mechanisms of triplet repeat diseases. Advantages of using C. elegans as a model system include the ease of genetic manipulation, the sequenced genome, and a short life cycle. Furthermore, researchers can precisely identify specific neurons and follow their development or survival throughout the animal’s lifetime. This chapter describes the tools and approaches for modeling triplet repeat diseases in C. elegans with a specific emphasis on polyglutamine (polyQ) diseases. Although the bulk of the chapter is devoted to generating a polyQ disease model in C. elegans , it also addresses potential avenues for assessing the impact of specific candidate genes/pathways on the disease process, including cell death and aging.