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Show THE UNIVERSITY OF UTAH HONORS COLLEGE MODELING NEURODEGENERATION AND ADRENOLEUKODYSTROPHY IN DROSOPHILA Erin Gavin (Anthea Letsou, Hannah Gordon) Department of H u m a n Genetics University of Utah Adrenoleukodystrophy is a progressive human genetic disorder that results in neurodegen-eration hypothesized to be due to improper metabolism of very long chain fatty acids (VL-CFAs). The Drosophila model used to study this disorder involves null mutants of the genes bubblegum (bgm) and double bubble (dbb), both of which are believed to function prior to the elongation and degradation of VLCFAs. Several approaches were employed to assess the value of bgm and dbb mutants as models for Adrenoleukodystrophy: (1) In yeast expression assays, we demonstrated that both the b g m and dbb gene products function as synthetases thereby activating long and very long chain fatty acids for further modification; (2) In in situ hybridization studies, w e identified the cells in which b g m and dbb are expressed; (3) In analyses of cryo and plastic sections of Drosophila heads, w e characterized cellular consequences of neurodegeneration in the brains and optic lobes of single and double mutant flies; (4) In physical assays, w e measured behavioral differences in mutant and wild-type flies which will serve as a live phenotype for a drug screen to identify potential therapies for Adrenoleukodystrophy in future experiments, and (5) In high fat diet studies, w e began to parse out the respective roles of b g m and dbb through their differential phenotypes after being raised on a high fat diet. The results of these pursuits serve to reinforce the value of the b g m and dbb mutants as models for Adrenoleukodystrophy, and to provide insight into the investigation of the etiology of neurodegeneration caused by improper metabolism of VLCFAs. Anthea Letsou 211 |