David B. Morton
Date of Award
Bachelor of Science (B.S.) in Science and University Honors
Exons (Genetics), Amyotrophic lateral sclerosis, Drosophila melanogaster -- Genetics -- Case studies, RNA splicing
Defects in the TAR DNA-binding protein named TDP-43 are known to be involved with many neurodegenerative diseases, including ALS. TBPH, a TDP-43 Drosophila orthologue is used to explore the specifics of those defects. This protein is known to have many cellular roles, one of them being a regulator for splicing. TBPH null flies have shown that the region coding for the voltage gated calcium channel cacophony is a potential target for splicing, directly producing a greater number of transcripts that lack exon 7. In this report, the phenotype of adult flies that lack exon 7 is explored. These mutants are known to have reduced larval crawling and decreased expression of cacophony. In this study exon 7(-) adult flies exhibit reduced activity compared to wild type flies as well as a decreased ability to survive exposure to caffeine. These phenotypes were rescued by a duplication of the cacophony genome. Driving cacophony selectively in neurons with different UAS-GAL4 drivers as a followup experiment is discussed with preliminary data.
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Ahrar, Jasmine E., "Exploring the Function of Exon 7 in Drosophila Cacophony in Relation to ALS" (2017). University Honors Theses. Paper 423.