Journal ArticleDOI
129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal.
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TLDR
The use of a different targeting strategy is reported, to produce inbred mice with a complete absence of both PrP protein and mRNA sequences, which are being used in experiments designed to address the role of PrP in the pathogenesis of scrapie and the replication of infectivity.Abstract:
The neural membrane glycoprotein PrP is implicated in the pathogenesis of the transmissible spongiform encephalopathies; however, the normal function of PrP and its precise role in disease are not understood. Recently, gene targeting has been used to produce mice withneo/PrP fusion transcripts, but no detectable PrP protein in the brain (1). Here we report the use of a different targeting strategy, to produce inbred mice with a complete absence of both PrP protein and mRNA sequences. At 7 mo of age, these mice show no overt phenotypic abnormalities despite the normal high levels of expression of PrP during mouse development. The mice are being used in experiments designed to address the role of PrP in the pathogenesis of scrapie and the replication of infectivity.read more
Citations
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Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
TL;DR: The cellular prion protein (PrPC) is identified as an amyloid-β-oligomer receptor by expression cloning, and PrPC-specific pharmaceuticals may have therapeutic potential for Alzheimer’s disease.
Journal ArticleDOI
The cellular prion protein binds copper in vivo
David R. Brown,Kefeng Qin,Jochen Herms,Axel Madlung,Jean Manson,Robert Strome,Paul E. Fraser,T. P. A. Kruck,A von Bohlen,Walter J. Schulz-Schaeffer,Armin Giese,David Westaway,Hans A. Kretzschmar +12 more
TL;DR: Findings indicate that PrPC can exist in a Cu-metalloprotein form in vivo, and that its amino terminus contains the octapeptide PHGGGWGQ, which is among the best-preserved regions of mammalian PrPC.
Journal ArticleDOI
Prion protein biology.
TL;DR: This research was supported by grants from the National Institute of Aging and the National institute of Neurologic Diseases and Stroke of the National Institutes of Health, International Human Frontiers of Science Program, and American Health Assistance Foundation, as well as by gifts from the Sherman Fairchild Foundation, Keck Foundation, G. Mathers Foundation, Bernard Osher Foundation, and Centeon.
Journal ArticleDOI
Normal host prion protein necessary for scrapie-induced neurotoxicity
Sebastian Brandner,Stefan Isenmann,Alex Raeber,Marek Fischer,Andreas W. Sailer,Yasushi Kobayashi,Silvia Marino,Charles Weissmann,Adriano Aguzzi +8 more
TL;DR: In addition to being resistant to scrapie infection, brain tissue devoid of PrPc is not damaged by exogenous PrPSc, and even 16 months after inoculation no pathological changes were seen in PrP-deficient tissue, not even in the immediate vicinity of the grafts.
References
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Journal ArticleDOI
Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques
Michael R. Scott,Dallas Foster,Carol Mirenda,Dan Serban,Frank Coufal,Monika Wälchli,Marilyn Torchia,Darlene Groth,George A. Carlson,Stephen J. DeArmond,David Westaway,Stanley B. Prusiner +11 more
TL;DR: It is argued that the PrP gene modulates scrapie susceptibility, incubation times, and neuropathology, and synthesis of infectious scrapie prions programmed by a recombinant DNA molecule is demonstrated.
Journal ArticleDOI
Spontaneous neurodegeneration in transgenic mice with mutant prion protein.
Karen K. Hsiao,Michael R. Scott,Dallas Foster,Darlene Groth,Stephen J. DeArmond,Stanley B. Prusiner +5 more
TL;DR: Many of the clinical and pathological features of Gerstmann-Straussler-Scheinker syndrome are reproduced in transgenic mice containing a prion protein with a single amino acid substitution, illustrating that a neurodegenerative process similar to a human disease can be genetically modeled in animals.
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Distinct prion proteins in short and long scrapie incubation period mice
David Westaway,Patricia A. Goodman,Carol Mirenda,Michael P. McKinley,George A. Carlson,Stanley B. Prusiner +5 more
TL;DR: The correlation of PrP sequence with length of scrapie incubation period suggests, but does not formally prove, congruency between Prn-p and PrN-i.
Journal ArticleDOI
Identification of a gene which controls the incubation period of some strains of scrapie agent in mice.
TL;DR: A gene in mice which controls the incubation period of the ME7 scrapie agent has been identified and the name “sinc”, to denote scrapie incubation time, is proposed and the two alleles which show no dominance are designated s7 for the one which shortens the incubated period and p7 forThe one which prolongs it.
Journal Article
Scrapie prion proteins are synthesized in neurons.
TL;DR: The authors found that prion proteins are synthesized almost exclusively within neurons, and the finding of PrP mRNA in neurons may explain the degeneration and vacuolation that occurs in these cells during scrapie infection.