Localization of CTG-Repeat-Containing Transgenes in Drosophila melanogaster Myotonic Dystrophy Models
Date of Award
Bachelor of Science
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Myotonic Dystrophy Type 1, DM1, is a multi-systemic muscle wasting disorder that results from expression of expanded CTG repeats in the DMPK gene in humans. Three transgenic Drosophila melanogaster lines have been created containing 60, 250, or 480 CTG repeats to model DM1. The transgenic repeats are expressed using the GAL4/UAS system. Expression of long-repeat transgenes ((CTG)250 and i(CTG)480) produces phenotypes consistent with DM1, relative to control lines ((CTG)60). The precise chromosomal location of insertion of the transgenes has not been reported. We used classical genetic approaches to localize CTG-repeat transgene insertion to a specific chromosome. We used GAL4 drivers with known locations to drive expression of repeats and assessed eye color phenotypes of the F2 generation. Results from the genetic analysis suggest that the (CTG)250 and i(CTG)480 transgene are likely localized to chromosome 2 and the (CTG)60 transgene is likely localized to chromosome 3. Knowing the location of the transgenes can allow for more practical mating schemes to study DM1 disease mechanisms, as well as provides crucial information for understanding transgene expression. The climbing velocity and flight capability tests were used to look at the effect of different drivers on muscle performance. The Mef2-GAL4 driver had the largest statistical difference in the climbing velocity test and the Hsp70-GAL4 driver had the largest statistical differences in the flight capability. These drivers should be chosen to improve the physiological differences seen in DM1 flies in future studies utilizing these tests. With the CTG repeat transgenes localized to a respective chromosome, researchers can better utilize these models to investigate disease mechanisms and potential treatments for DM1.
Waltrip, Andrea, "Localization of CTG-Repeat-Containing Transgenes in Drosophila melanogaster Myotonic Dystrophy Models" (2023). Student Research Submissions. 511.
Disease Modeling Commons, Genetics Commons, Laboratory and Basic Science Research Commons, Musculoskeletal Diseases Commons