Investigation of RNA Binding Protein Pumilio as a Genetic Modifier of Mutant CHMP2B in Frontotemporal Dementia (FTD): A Masters Thesis
Authors
Du, XingFaculty Advisor
Andreas BergmannAcademic Program
Interdisciplinary Graduate ProgramUMass Chan Affiliations
Molecular, Cell and Cancer Biology DepartmentDocument Type
Master's ThesisPublication Date
2016-08-14Keywords
Theses, UMMSFrontotemporal Dementia
RNA-Binding Proteins
Endosomal Sorting Complexes Required for Transport
Frontotemporal Dementia
RNA-Binding Proteins
Endosomal Sorting Complexes Required for Transport
Biochemistry
Genetics and Genomics
Medical Genetics
Molecular Biology
Nervous System Diseases
Metadata
Show full item recordAbstract
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.DOI
10.13028/M27C7RPermanent Link to this Item
http://hdl.handle.net/20.500.14038/32219Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/M27C7R