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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Journal ArticleDOI
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
Paradoxical shortening of scrapie incubation times by expression of prion protein transgenes derived from long incubation period mice
David Westaway,Carol Mirenda,Dallas Foster,Yeganeh Zebarjadian,Michael R. Scott,Marilyn Torchia,Shu-Lian Yang,Hana Serban,Stephen J. DeArmond,Christine Ebeling,Stanley B. Prusiner,George A. Carlson +11 more
TL;DR: In this paper, the authors analyzed the effect of the ILnJ Prn-p b allele and a distinct incubation time locus designated as PRn-i on scrapie incubation times.
Journal ArticleDOI
Three hamster species with different scrapie incubation times and neuropathological features encode distinct prion proteins.
D H Lowenstein,Darel A. Butler,David Westaway,Michael P. McKinley,Stephen J. DeArmond,Stanley B. Prusiner +5 more
TL;DR: Differences within the PrP open reading frame that uniquely distinguish the three hamster species are within a hydrophilic segment of 11 amino acids that includes polymorphisms linked to scrapie incubation times in inbred mice and an inherited prion disease of humans.
Journal ArticleDOI
Use of BRL-conditioned medium in combination with feeder layers to isolate a diploid embryonal stem cell line
TL;DR: The modifications to the ES cell isolation procedure described here may improve the efficiency with which karyotypically normal lines can be derived.
Journal ArticleDOI
Genetic ablation of a mouse gene expressed specifically in brain.
David M. Kingsley,Eugene M. Rinchik,Liane B. Russell,H.P. Ottiger,J G Sutcliffe,Neal G. Copeland,Nancy A. Jenkins +6 more
TL;DR: It is shown that the mouse 1B1075 gene is located between the dilute (d) and short ear (se) genes on chromosome 9, and this results provide a new molecular entry point for detailed characterization of other genes in the d‐se region.
Book ChapterDOI
The scrapie fibril protein and its cellular isoform.
Jayne Hope,Jean Manson +1 more
TL;DR: Proteins need help to fold and attain their functional conformation, and mechanisms fail to prevent the formation of protease-resistant, misfolded forms of PrP during the development of scrapie and other transmissible spongiform encephalopathies, and PrP is a biochemical marker of these diseases.