Interactions between Amyloid Precursor Protein and Prion Protein Impact Cell Adhesion and Apoptosis in the Developing Zebrafish

  • Author / Creator
    Kaiser, Darcy
  • We report here that knockdown of either amyloid precursor protein (APP) or prion protein (PrP) in the zebrafish produces an overt dose-dependent phenotype characterized by systemic morphological defects and CNS cell death. We report findings that the zebrafish PrP-1 gene genetically interacts with one, but not the other, zebrafish APP gene paralog. The interaction proves specific to these genes and human and mouse mRNAs can rescue the observed phenotypes, highlighting conserved functions. We find apoptotic labeling increased and aggregating ability of cells decreased when either of these genes is substantially knocked down, or sub-effective knock down of each gene is combined. Using a cell mixing paradigm we further provide evidence that the interaction occurs in a cell autonomous fashion. Our study is the first to report an in vivo interaction between these two genes, which could prove invaluable to the design and screening of therapeutics.

  • Subjects / Keywords
  • Graduation date
    Fall 2011
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Specialization
    • Molecular Biology and Genetics
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • David Westaway, Medicine and Dentistry
    • W. Ted Allison, Biological Sciences
    • Andrew Waskiewicz, Biological Sciences