dc.contributor.author |
Johnson, Abbey Lin Gillispie |
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dc.date.accessioned |
2017-10-11T22:41:24Z |
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dc.date.available |
2017-10-11T22:41:24Z |
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dc.date.issued |
2017 |
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dc.identifier.uri |
http://hdl.handle.net/1794/22860 |
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dc.description |
46 pages. A thesis presented to the Department of Biology and the Clark Honors College of the University of Oregon in partial fulfillment of the requirements for degree of Bachelor of Science, Spring 2017 |
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dc.description.abstract |
Usher Syndrome (USH) is the leading cause of hereditary deafblindness. It is characterized by hearing and vestibular impairment as well as progressive retinal degeneration. This syndrome has been classified into three types based on the severity of the symptoms. Patients affected with USH1 present the most severe symptoms. CADHERIN 23 (CDH23), the focus of this research, is one of the 6 genes causing USH1 when mutated. Previous work in zebrafish has determined that the encoded protein is present in an USH1 complex that preassembles at the endoplasmic reticulum (ER), a subcellular compartment. When the cdh23 gene is mutated, the USH1 complex assembly and trafficking are disrupted, which leads to a cellular response called ER stress. It was also shown that inner ear hair cell and retinal cell death increase in the cdh23 mutants. As a first step to understand if ER stress is the cause of increased cell death in the cdh23 zebrafish mutants, I characterized the molecular pathways activated by ER stress and tested if FDA approved drugs targeting specific components of the activated pathways could lower ER stress and decrease cell death. I found that the Ire1 pathway is potentially activated in the inner ear hair cells and that the Perk pathway is activated in both the inner ear hair cells and the retinal cells of cdh23 mutants. Furthermore, these mutants showed decreased levels of ER stress when treated with FDA approved drugs. The preliminary data presented in this thesis expand the current understanding of the molecular mechanism leading to USH1 and point toward directions for future research. |
en_US |
dc.language.iso |
en_US |
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dc.publisher |
University of Oregon |
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dc.rights |
Creative Commons BY-NC-ND 4.0-US |
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dc.subject |
Usher Syndrome |
en_US |
dc.subject |
Zebrafish |
en_US |
dc.subject |
ER Stress |
en_US |
dc.subject |
Unfolded protein response |
en_US |
dc.subject |
Vestibular system |
en_US |
dc.subject |
Visual system |
en_US |
dc.title |
Identification of the Molecular Pathways Affected in Usher Syndrome Type 1 Using Zebrafish as an Animal Model |
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dc.type |
Thesis/Dissertation |
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