title: Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein.
abstract: Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease approximately 200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrPSc (where PrPSc is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrPSc. The patterns of MHu2MPrPSc and MoPrPSc accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease > 500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.
authors.affiliation: Department of Neurology, University of California, San Francisco 94143.
authors.forename: G C
authors.initials: GC
authors.lastname: Telling
authors.forename: M
authors.initials: M
authors.lastname: Scott
authors.forename: K K
authors.initials: KK
authors.lastname: Hsiao
authors.forename: D
authors.initials: D
authors.lastname: Foster
authors.forename: S L
authors.initials: SL
authors.lastname: Yang
authors.forename: M
authors.initials: M
authors.lastname: Torchia
authors.forename: K C
authors.initials: KC
authors.lastname: Sidle
authors.forename: J
authors.initials: J
authors.lastname: Collinge
authors.forename: S J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction / Q000379:methods; D011328:Prions / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000096:biosynthesis*; D015183:Restriction Mapping; D013997:Time Factors
chemical_list: D011328:Prions; D011993:Recombinant Fusion Proteins