Undergraduate Research at FIU (URFIU) Conference

Effects of temozolomide on the expanded GAA repeats in Friedreich's ataxia transgenic mice

Congenital hydrocephalus is a life-threatening condition resulting from cerebrospinal fluid build-up in brain ventricles. The mechanisms underlying the disease are unknown and there are limited available therapies. Mutations in the L1 gene, encoding a neuronal cell adhesion molecule, cause hydrocephalus. Interestingly, siblings with the same L1 mutation can present the disease with varying severity levels, suggesting the presence of genetic modifiers. Identifying such genetic L1 interactors in mammals is difficult because of their complex genome. With a single L1 homolog, sax-7, a simple genome, and well established genetic tools, Caenorhabditis elegans is an accessible model system to identify such interactions. The lab previously identified a genetic interaction between sax-7 and ras, resulting in a synthetic phenotype that correlates with a fluid homeostasis defect. Consistent with the excretory system playing a role in fluid regulation in C. elegans, sax-7 ras double mutant adults display defects in the excretory canal, the major cell in the excretory system. The aim of this project is to determine whether the excretory canal abnormality is due to developmental or maintenance defects by examining its presence in younger animals. A Green Fluorescent Protein (GFP) marker was crossed into the worms in order to visualize canals under a fluorescent microscope. Our results showed that there is a statistically significant difference in excretory canal lengths between sax-7(0) ras(gf), and the other three worm strains observed. This data suggests that the shortening is caused by a developmental defect. Future experiments should look at L1 and L2 staged worms to make a thorough conclusion.