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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Prion and prejudice: normal protein and the synapse
TL;DR: There is increasing evidence that the normal prion protein binds copper and the resulting complex possesses anti-oxidant activity, and that this, in turn, might have vital implications for synaptic homeostasis.
Journal ArticleDOI
Mammalian prions and their wider relevance in neurodegenerative diseases
TL;DR: Insight is provided into the usefulness and limitations of prion analogies and their aetiological and therapeutic relevance in brain diseases involving the deposition of assemblies of misfolded proteins in the brain.
Journal ArticleDOI
The biological function of the cellular prion protein: an update
TL;DR: The proposed physiological roles of PrPC in the central and peripheral nervous systems are revisited and the need for their critical reassessment using new, rigorously controlled animal models is highlighted.
Journal ArticleDOI
Increased levels of oxidative stress markers detected in the brains of mice devoid of prion protein
Boon Seng Wong,Tong Liu,Ruliang Li,Tao Pan,Robert B. Petersen,Mark A. Smith,Pierluigi Gambetti,George Perry,Jean Manson,David R. Brown,Man Sun Sy +10 more
TL;DR: Higher levels of oxidative damage to proteins and lipids in the brain lysates of Prnp−/– as compared to wild‐type (WT) mice of the same genetic background are indicative of a role for PrP in oxidative homeostasis in vivo.
Journal ArticleDOI
Doxycycline control of prion protein transgene expression modulates prion disease in mice
Patrick Tremblay,Zeev Meiner,Maria Galou,Cornelia Heinrich,Chris Petromilli,Thomas S. Lisse,Juliana Cayetano,Marilyn Torchia,William C. Mobley,Hermann Bujard,Stephen J. DeArmond,Stanley B. Prusiner +11 more
TL;DR: Use of the tTA system to control PrP expression allowed production of Tg mice with high levels of PrP that otherwise cause many embryonic and neonatal deaths, indicating that low levels ofPrPSc can be tolerated.
References
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Journal ArticleDOI
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
TL;DR: A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described, providing a pure preparation of undegraded RNA in high yield and can be completed within 4 h.
Journal ArticleDOI
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Lawrence A. Donehower,Michele Harvey,Betty L. Slagle,Mark J. McArthur,Charles A. Montgomery,Janet S. Butel,Allan Bradley +6 more
TL;DR: Observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
Journal ArticleDOI
Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells.
Kirk R. Thomas,Mario R. Capecchi +1 more
TL;DR: This work mutated, by gene targeting, the endogenous hypoxanthine phosphoribosyl transferase (HPRT) gene in mouse embryo-derived stem (ES) cells and compared the gene-targeting efficiencies of two classes of neor-Hprt recombinant vectors.
Journal ArticleDOI
Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein
Hansruedi Büeler,Marek Fischer,Yolande Lang,Yolande Lang,Horst Bluethmann,Horst Bluethmann,Hans-Peter Lipp,Stephen J. DeArmond,Stephen J. DeArmond,Stanley B. Prusiner,Stanley B. Prusiner,Michel Aguet,Charles Weissmann +12 more
TL;DR: It is now feasible to determine whether mice devoid of PrPc can propagate prions and are susceptible to scrapie pathogenesis.
Journal ArticleDOI
Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene.
Li Kuo Su,Kenneth W. Kinzler,Bert Vogelstein,Antoinette C. Preisinger,Amy R. Moser,Cindy Luongo,Karen A. Gould,William F. Dove +7 more
TL;DR: In this paper, a mouse lineage that exhibits an autosomal dominantly inherited predisposition to multiple intestinal neoplasia (Min) was described and linkage analysis showed that the murine homolog of the APC gene (mApc) was tightly linked to the Min locus.