NR AUGU
AU Bian,J.; Nazor,K.E.; Angers,R.C.; Jernigan,M.; Seward,T.; Centers,A.P.; Green,M.; Telling,G.C.
TI GFP-tagged PrP supports compromised prion replication in transgenic mice
QU Biochemical and Biophysical Research Communications 2006 Feb 17; 340(3): 894-900
PT journal article
AB The ability of green fluorescent protein (GFP)-prion protein (PrP) fusions to support prion propagation has not been demonstrated. Here, we show that while transgenic mice expressing PrP tagged at its amino terminus with enhanced GFP, referred to as EGFPrP-N, supported prion replication, disease onset was prolonged, the brains of diseased mice did not exhibit typical disease neuropathology and disease-associated EGFPrP-N lacked the full spectrum of biochemical properties normally associated with PrPsc. Co-expression of wild-type PrP and EGFPrP-N substantially reduced prion incubation times and resulted in accumulation of protease-resistant EGFPrPsc-N in the brains of transgenic mice as well as chronically infected cultured cells, suggesting that wild-type PrP rescued a compromised amino terminal function in EGFPrP-N. While our results show that EGFPrPc-N adopts a conformation necessary for the production of infectious prions, the synergistic interaction of wild-type and EGFPrP-N underscores the importance of the amino terminus in modulating prion pathogenesis.
MH Animals; Brain/metabolism; Cells, Cultured; DNA Replication; Genetic Techniques; Green Fluorescent Proteins/chemistry/*metabolism; Mice; Mice, Transgenic; Microscopy, Fluorescence; Prions/chemistry/*genetics; Protein Conformation; Protein Structure, Tertiary; Recombinant Fusion Proteins/chemistry; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
AD Rachel Angers, Michael Jernigan, Adrian Centers, Glenn C. Telling, Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA; Karah E. Nazor*, Glenn C. Telling, Graduate Center for Gerontology, University of Kentucky, Lexington, KY 40536, USA; Jifeng Bian*, Tanya Seward, Adrian Centers, Glenn C. Telling, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA; Glenn C. Telling (gtell2@uky.edu), Department of Neurology, University of Kentucky, Lexington, KY 40536, USA; Michael Green, UK Transgenic Facility, University of Kentucky, Lexington, KY 40536, USA; Karah E. Nazor*, Present address: Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143-0518, USA; * These authors contributed equally.
SP englisch
PO USA