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Expanding a Drosophila Model of Fetal Alcohol Spectrum Disorder: A Forward Genetic Screen for Developmental Ethanol Exposure Phenotypes
Thesis - Campus Access Only
Master of Science (MS)
Biology; Genetics; Molecular biology
Fetal alcohol spectrum disorder (FASD), a condition resulting from maternal consumption of ethanol during pregnancy, can result in a wide range of effects including reduced viability, growth deficiency, neurocognitive abnormalities, impaired motor functions, and behavior problems. Previous research focusing on the role of the insulin signaling pathway has established Drosophila melanogaster as a model for FASD. Here I describe a forward genetic screen undertaken with the goal of expanding this Drosophila FASD model. We generated approximately 850 new mutant strains of Drosophila using P element mutagenesis. We then screened them for atypical rates of lethality and delay when exposed to ethanol during larval and pupal development. After more rigorous screens confirming the phenotype in a subset of these strains, we used inverse PCR and bioinformatic analysis to identify the genes most likely affected. This process has so far yielded 30 promising mutant strains and enabled us to identify several new genes mediating developmental ethanol toxicity. One new avenue of research opened by the screen is a model linking FASD to lipid dysregulation and subsequent oxidative stress. We have also identified several genes linking ethanol toxicity to mechanisms of central nervous system development, which will again add to the robustness of the model.
Lafler, Janet, "Expanding a Drosophila Model of Fetal Alcohol Spectrum Disorder: A Forward Genetic Screen for Developmental Ethanol Exposure Phenotypes" (2015). Master's Theses. 4593.