NR AOSP
AU Flechsig,E.; Hegyi,I.; Leimeroth,R.; Zuniga,A.; Rossi,D.; Cozzio,A.; Rülicke,T.; Götz,J.; Aguzzi,A.; Weissmann,C.
TI Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-104
PT Konferenz-Poster
AB The physiological function of the cellular prion protein PrP is still elusive. Several PrP knockout mouse lines have been generated, differing in the design of the gene disruption. Two lines in which only the PrP coding sequence was disrupted, referred to as "Zürich-I-type" mice, developed normally and remained healthy, showing only minor electrophysiological deficits and altered circadian rhythm. However, three other lines with more extensive gene deletions, "Nagasaki-type" PrP knockout mice, developed Purkinje cell loss and ataxia. The ataxic phenotype has been associated with ectopic expression of Doppel (Dpl) in brain, particularly in Purkinje cells. Surprisingly, the phenotype is abrogated by co-expression of full-length PrP. Dpl is 25 % similar to PrP, has the same globular fold, but lacks the flexible N-terminal region. We targeted PrP devoid of the flexible N-terminal region (PrPdel32-134) specifically to Purkinje cells of Zürich-I-type PrP knockout mice and found that the resulting phenotype was the same as that of Nagasaki-type PrP knockout mice with ectopic expression of Dpl, namely Purkinje cell loss and ataxia that are reversed by PrP. Dpl and truncated PrP likely cause Purkinje cell degeneration by the same mechanism.
AD E. Flechsig, Institute of Virology and Immunbiology, University of Würzburg, 97078 Würzburg, Germany; I. Hegyi, A. Aguzzi, Institute of Neuropathology, University Zürich, 8091 Zürich, Switzerland; E. Flechsig, R. Leimeroth, A. Zuniga, D. Rossi, A. Cozzio, J. Götz, C. Weissmann, Institute of Molecular Biology I, University of Zürich, 8057 Zürich, Switzerland; E. Flechsig, T. Rülicke, C. Weissmann, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK
SP englisch
PO Deutschland