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
A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse
TL;DR: In a pedigree derived from a mouse treated with the mutagen ethylnitrosourea, a mutation has been identified that predisposes to spontaneous intestinal cancer.
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A cellular gene encodes scrapie PrP 27-30 protein
Bruno Oesch,Bruno Oesch,David Westaway,Monika Wälchli,Monika Wälchli,Michael P. McKinley,Stephen B. H. Kent,Stephen B. H. Kent,Ruedi Aebersold,Ruedi Aebersold,Ronald A. Barry,Paul Tempst,Paul Tempst,David B. Teplow,David B. Teplow,Leroy Hood,Leroy Hood,Stanley B. Prusiner,Stanley B. Prusiner,Charles Weissmann,Charles Weissmann +20 more
TL;DR: A clone encoding PrP 27-30, the major protein in purified preparations of scrapie agent, was selected from a scrapie-infected hamster brain cDNA library by oligonucleotide probes corresponding to the N terminus of the protein.
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HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells.
TL;DR: The realization of this possibility by the selection in vitro of variant ES cells deficient in hypoxanthine guanine phosphoribosyl transferase is reported, leading to their use to produce germline chimaeras resulting in female offspring heterozygous for HPRT-deficiency, and the generation of HPRt-deficient preimplantation embryos from these females.
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Scrapie prion protein contains a phosphatidylinositol glycolipid
TL;DR: Observations indicate that PrPC is anchored to the cell surface by the glycolipid, which is derived from PrPSc by limited proteolysis at the amino terminus.
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β2-Microglobulin deficient mice lack CD4 − 8 + cytolytic T cells
TL;DR: For example, this article showed that mice homozygous for a beta 2-microglobulin gene disruption do not express any detectable beta 2m protein on the cell surface, yet are fertile and apparently healthy.