College of Arts & Sciences
Hereditary Spastic P araplegia and the Spastin Gene
K ave esh K utty COAS Biological Sciences
Dr . D anie l Ma renda Faculty Mentor Biology
Poster Session A
Hereditary Spastic Paraplegia (HSP) is a neurological disease that causes spastic weakness in an organism’s lower extremities, and can lead to axonal degeneration. Although over twenty genes have been linked to HSP in humans, the Spastin gene is responsible for more than 40% of all cases. The Spastin gene codes for a protein responsible primarily for microtubule severing. Mutants of the spastin protein are responsible for HSP. The two mutants of spastin studied are M1 and M87; both of these mutants form protein aggregates that cause HSP. The M1 isoform of spastin has been found to be more neurotoxic than the M87 isoform. Drosophila melanogaster is our model organism. Using behavioral assays, as well as analyzing the neuromorphology of the larval neuromuscular junction, the differences in effect between the presence of M1, M87, and Spastin knockdowns will be assessed. The analysis of Spastin knockdowns will reveal whether the aggregation of mutant M1 and M87 causes a more detrimental result than Spastin knockouts. After observing flies with Spastin-RNAi knockdowns, M1, or M87, we expect to observe the most neurotoxic aggregation of the mutant M1 form along the ventral nerve cord, followed by M87 and then Spastin-RNAi in a decreasing order of severity. 32