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Type: Theses
Title: Identifying the pathological changes caused by familial Alzheimer’s disease-like mutations in zebrafish psen2
Author: Jiang, Haowei
Issue Date: 2018
School/Discipline: School of Biological Sciences
Abstract: This project aimed to investigate the pathological changes caused by familial Alzheimer's disease-related (fAD-related) mutations in the gene PSEN2 based on a zebrafish model system. The CRISPR/Cas9 system was used to generate fAD-like mutations in the zebrafish genome. Although this mutagenesis system failed to generate mutations directly equivalent to the fAD mutations Nl411 and Vl481, (Nl40I and Vl471 in zebrafishpsen2), a fAD-like mutation psen2T141_L142delinsMISLISV [T141_L142delinsMISLISV superscript], a truncation mutation psen2N140fs [N140fs superscript], and a putative null mutation psen2S4Ter [S4Ter superscript], were generated. Allele­ specific expression tests using digital quantitative PCR were applied to all three mutations, and nonsense mediated decay was found to occur for the psen2N140fs [N140fs superscript] transcript. RNA-seq-based transcriptomic analysis was performed on brains from psen2S4Ter [S4Ter superscript] heterozygous and wild type siblings from a single family and revealed a likely relationship between psen2 and mitochondrial formation and function, which are thought to be associated with AD pathology. A GFP-Lc3a-GFP construct was designed to assay changes in autophagic flux in zebrafish larvae. By applying this assay to psen2S4Ter [S4Ter superscript]-carrying mutant larvae, as well as larvae possessing mutations in psen1, the Psen2 protein was seen to play a role in autophagy, which is also thought to be a process important in the development of AD pathology. Thus, the results of this project may contribute to a better understanding of the pathological mechanisms underlying AD.
Advisor: Lardelli, Michael Trent
Newman, Morgan
Dissertation Note: Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Biological Sciences, 2018
Keywords: Research by publication
familial Alzheimer’s disease
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at
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