Date of Award
12-2024
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Genetics and Biochemistry
Committee Chair/Advisor
Dr. Robert Anholt
Committee Member
Dr. Trudy Mackay
Committee Member
Dr. Lela Lackey
Committee Member
Dr. Richard Steet
Abstract
Mucopolysaccharidosis IIIA (MPS IIIA) is a rare lysosomal storage disorder that arises from inability to break down heparan sulfate (HS) because of mutations in the N-sulfoglucosamine sulfohydrolase (SGSH) gene. We used a deletion mutant of the Drosophila melanogaster Sgsh gene along with three point mutations analogous to mutations observed in patients (S64W, L89P, S301P) to show an increase in the average percent of area with lysosomal puncta in the fly brains of our mutants using Lysotracker. RNA sequencing of brains of mutant and control flies showed 441 (Knockout), 337 (S64W), 155 (L89P), and 96 (S301P) differentially expressed genes, including N-acetyl-alpha-glycosaminidase (Naglu) and N-acetylglucosamine 6-Sulfatase (GNS), which are both downstream from Sgsh in the HS catabolic pathway. Disruption of Sgsh expression impacts multiple interrelated biological processes, including developmental pathways, transcriptional regulation, RNA processing and nuclear transport, ribosome biogenesis, protein folding and proteolysis, metabolic pathways, and neurodevelopment. These observations indicate that D. melanogaster can serve as a model for MPS IIIA and lay the foundation for future comparative genomics approaches to assess the impact of background modifiers on variation in disease severity and penetrance.
Recommended Citation
Bishop, Rebecca, "A Drosophila Model of Mucopolysacchridosis IIIA" (2024). All Theses. 4433.
https://open.clemson.edu/all_theses/4433
