NR AOYH
AU Rivera-Milla,E.; Oidtmann,B.; Stuermer,C.A.O.; Bauer,M.; Malaga-Trillo,E.
TI Molecular characterization of duplicated fish prion genes and their roles during zebrafish development
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-46
PT Konferenz-Poster
AB Infectious prion proteins (PrP) cause a group of lethal neurodegenerative diseases in mammals due to the acquisition of an aberrant conformation. Because of its unique pathogenic features, PrP is one of the most intensively studied proteins; however, little is known about its normal function. Here we report the identification of the first prion gene homologues in fish: two (duplicated) genes in Fugu (PrP-a and PrP-b), zebrafish, salmon and trout. Comparative analysis of PrP sequences shows rapid rates of molecular evolution between different vertebrate classes, as well as molecular stasis within each class. Among all vertebrate groups, the highest intragroup divergence is observed within fishes. Although fish and tetrapod PrP genes have low sequence similarity, they share the presence of an N-terminal repetitive region and a globular domain at the C-terminus, among other conserved structural landmarks. Since the two PrP genes of zebrafish and Fugu are located in large -paralogous- genomic contigs, it would seem that they arose during the teleost-specific genome duplication. We confirmed this assumption by analyzing the gene content and order of these chromosomal regions, and comparing them to their mammalian counterparts. To uncover the natural function of PrPs, we analyzed their expression patterns in developing zebrafish by means of RNA in situ hybridization, and found that both prion mRNAs are transcribed early in embryogenesis, particularly restricted to differentiating neural tissue. We also microinjected mRNAs into 1-cell embryos and found remarkable head phenotypes resulting from PrP overexpression. Our results provide evidence for an early developmental role of PrPc, and set the stage for the molecular dissection of protein domains associated with its normal function, as well as the evolution of its conversion and aggregation capabilities.
AD Eric Rivera-Milla, Claudia. A.O. Stuermer, Edward Málaga-Trillo, University of Konstanz, Germany; Birgit Oidtmann, Ludwig-Maximilians-University, Germany; Michael Bauer, Robert Koch Institute, Germany
SP englisch
PO Deutschland