NR ATIK
AU Saghafi,S.; Tremblay,P.; Spilman,P.; DeArmond,S.J.; Prusiner,S.B.; Lingappa,V.R.
TI Developmental Dysregulation of PrPc Results in Transmembrane PrP Expression and Severe Neurodegenration
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-42
PT Konferenz-Poster
AB An inducible Tet-off system was used to investigate the role of PrP during brain maturation of mice. Mice taken of doxycycline at post natal day 21 to induce expression of PrP develop severe and rapid neurodegeneration. Substantial levels of apoptosis with massive infiltration by astrocytes was observed in most brain regions and radial Bargmann glia was observed in the cerebellum. In contrast mice kept on dox or mice constitutively expressing wildtype PrP showed no signs of neurodegenration. Analysis of brain homogenates revealed an explosive increase in type II transmembrane PrP, termed CtmPrP however remained undetectable upon constitutive expression. Our data suggests that temporal dysregulation of PrPc expression can have a dramatic effect on the distribution of topological isoforms, analogous to infection with PrPsc. Such mice are a powerful model system to investigate the mechanism by which elevated CtmPrP expression leads to disease.
AD S.Saghafi, P.Tremblay, P.Spilman, S.J.DeArmond, S.B.Prusiner, V.R.Lingappa, UCSF, USA
SP englisch
PO Deutschland