NR ATMT
AU Rivera-Milla,E.; Thomanetz,V.; Solis,G.P.; Stuermer,C.A.O.; Malaga-Trillo,E.
TI Towards a functional characterization of PrP using the zebrafish model
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Genetics, strains and emerging problems GEN-19
PT Konferenz-Poster
AB
Despite intensive research on mammalian models, basic questions about the biological role of prion proteins (PrP) and the evolutionary origin of prion disease remain largely unanswered. We previously characterized the genetic variation, expression, genomic context and structural evolution of duplicated PrP and PrP-related genes in fish, relative to other vertebrates. Here we used in situ hybridization to examine their expression patterns during zebrafish development, and performed translational knock-downs via microinjection of early embryos. Our results show clearly distinct spatiotemporal expression domains for PrP-1 and -2, which display early ubiquitous and late neural transcription profiles. Transient PrP-knockdown and RNA overexpression experiments result in severe phenotypes ranging from abnormal brain formation to lethal impairment of early development. We also generated GFP-fusion constructs to analyze the cellular localization of fish PrPs in vivo, as well as mouse-fish-PrP chimeric proteins to examine their functional equivalence with mammalian PrPs. Our developmental and comparative analysis provides new insights on the functional significance of PrP domains and opens up new possibilities for the experimental analysis of prion misfolding and neurodegeneration in a non-mammalian model like the zebrafish.
Supported by the DFG, TR-SFB11, MWK-BW and the DAAD.
AD Eric Rivera-Milla, Venus Thomanetz, Gonzalo P. Solis, Claudia A.O. Stuermer, Edward Málaga-Trillo, University of Konstanz, Germany
SP englisch
PO Deutschland