title: GFP-tagged PrP supports compromised prion replication in transgenic mice.
abstract: 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 PrP(Sc). Co-expression of wild-type PrP and EGFPrP-N substantially reduced prion incubation times and resulted in accumulation of protease-resistant EGFPrP(Sc)-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 EGFPrP(C)-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.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Bian
authors.forename: Karah E
authors.initials: KE
authors.lastname: Nazor
authors.forename: Rachel
authors.initials: R
authors.lastname: Angers
authors.forename: Michael
authors.initials: M
authors.lastname: Jernigan
authors.forename: Tanya
authors.initials: T
authors.lastname: Seward
authors.forename: Adrian
authors.initials: A
authors.lastname: Centers
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Telling
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D004261:DNA Replication; D005821:Genetic Techniques; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D011328:Prions / Q000737:chemistry / Q000235:genetics*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry
chemical_list: D011328:Prions; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins