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dc.contributor.advisorAndreas Bergmann
dc.contributor.authorDu, Xing
dc.date2022-08-11T08:08:46.000
dc.date.accessioned2022-08-23T16:07:17Z
dc.date.available2022-08-23T16:07:17Z
dc.date.issued2016-08-14
dc.date.submitted2016-11-28
dc.identifier.doi10.13028/M27C7R
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32219
dc.description.abstractFrontotemporal dementia (FTD) is the second most common early-onset dementia. A rare mutation in CHMP2B gene was found to be associated with FTD linked to chromosome 3. Previous studies have shown that mutant CHMP2B could lead to impaired autophagy pathway and altered RNA metabolism. However, it is still unknown what genes mediate the crosstalk between different pathways affected by mutant CHMP2B. Genetic screens designed to identify genes interacting with mutant CHMP2B represents a key approach in solving the puzzle. Expression of mutant CHMP2B (CHMP2Bintron5) in Drosophila eyes leads to a neurodegenerative phenotype including melanin deposition and disrupted internal structure of ommatidia. The phenotype is easily quantified by estimating the percentage of black dots on the surface of the eyes. Using this established Drosophila model, I searched for genes encoding RNA binding proteins that genetically modify CHMP2Bintron5 toxicity. I found that partial loss of Pumilio, a translation repressor, mitigates CHMP2Bintron5 induced toxicity in the fly eyes. Western blot analysis showed that down regulation of Pumilio does not significantly decrease CHMP2Bintron5 protein level, indicating indirect regulation involved in suppression of the phenotype. The molecular targets regulated by Pumilio and the mechanism underlying CHMP2Bintron5 toxicity suppression by Pumilio down-regulation requires further investigation.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectTheses, UMMS
dc.subjectFrontotemporal Dementia
dc.subjectRNA-Binding Proteins
dc.subjectEndosomal Sorting Complexes Required for Transport
dc.subjectFrontotemporal Dementia
dc.subjectRNA-Binding Proteins
dc.subjectEndosomal Sorting Complexes Required for Transport
dc.subjectBiochemistry
dc.subjectGenetics and Genomics
dc.subjectMedical Genetics
dc.subjectMolecular Biology
dc.subjectNervous System Diseases
dc.titleInvestigation of RNA Binding Protein Pumilio as a Genetic Modifier of Mutant CHMP2B in Frontotemporal Dementia (FTD): A Masters Thesis
dc.typeMaster's Thesis
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1857&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/846
dc.legacy.embargo2017-08-24T00:00:00-07:00
dc.identifier.contextkey9416786
refterms.dateFOA2022-08-30T03:48:23Z
html.description.abstract<p>Frontotemporal dementia (FTD) is the second most common early-onset dementia. A rare mutation in CHMP2B gene was found to be associated with FTD linked to chromosome 3. Previous studies have shown that mutant CHMP2B could lead to impaired autophagy pathway and altered RNA metabolism. However, it is still unknown what genes mediate the crosstalk between different pathways affected by mutant CHMP2B. Genetic screens designed to identify genes interacting with mutant CHMP2B represents a key approach in solving the puzzle. Expression of mutant CHMP2B (CHMP2Bintron5) in Drosophila eyes leads to a neurodegenerative phenotype including melanin deposition and disrupted internal structure of ommatidia. The phenotype is easily quantified by estimating the percentage of black dots on the surface of the eyes. Using this established Drosophila model, I searched for genes encoding RNA binding proteins that genetically modify CHMP2Bintron5 toxicity. I found that partial loss of Pumilio, a translation repressor, mitigates CHMP2Bintron5 induced toxicity in the fly eyes. Western blot analysis showed that down regulation of Pumilio does not significantly decrease CHMP2Bintron5 protein level, indicating indirect regulation involved in suppression of the phenotype. The molecular targets regulated by Pumilio and the mechanism underlying CHMP2Bintron5 toxicity suppression by Pumilio down-regulation requires further investigation.</p>
dc.identifier.submissionpathgsbs_diss/846
dc.contributor.departmentMolecular, Cell and Cancer Biology Department
dc.description.thesisprogramInterdisciplinary Graduate Program


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