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
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Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis
TL;DR: In vivo and in vitro studies find that PrP(c) is expressed in multipotent neural precursors and mature neurons but is not detectable in glia, and loss- and gain-of-function experiments demonstrate thatPrP( c) levels correlate with differentiation of multipotent Neural precursor into mature neurons in vitro and that PrPs positively influence neuronal differentiation in a dose-dependent manner.
Journal ArticleDOI
Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain
Daniela Rossi,Antonio Cozzio,Eckhard Flechsig,Michael A. Klein,Thomas Rülicke,Adriano Aguzzi,Charles Weissmann +6 more
TL;DR: Dpl levels in brain and onset of the ataxic syndrome are inversely correlated and a new PrP knockout line, ‘Zürich II’, with a 2.9 kb Prnp deletion developed this phenotype at ∼10 months (50% morbidity) and a single Prnp allele abolished the syndrome.
Journal ArticleDOI
Targeting Cellular Prion Protein Reverses Early Cognitive Deficits and Neurophysiological Dysfunction in Prion-Infected Mice
Giovanna R. Mallucci,Melanie D. White,Michael Farmer,A. Dickinson,Husna Khatun,Andrew D. Powell,Sebastian Brandner,John G. R. Jefferys,John Collinge +8 more
TL;DR: It is shown that cognitive and behavioral deficits and impaired neurophysiological function accompany early hippocampal spongiform pathology and can be rescued, supporting the concept that they are caused by a transient neurotoxic species, distinct from aggregated PrP(Sc).
Journal ArticleDOI
Prion protein and Aβ‐related synaptic toxicity impairment
Anna Maria Calella,Mélissa Farinelli,Mario Nuvolone,Mario Nuvolone,Osvaldo Mirante,Rita Moos,Jeppe Falsig,Isabelle M. Mansuy,Adriano Aguzzi +8 more
TL;DR: It is reported that ablation or overexpression of PrPC had no effect on the impairment of hippocampal synaptic plasticity in a transgenic model of AD, and the role of Pr PC as a mediator of Aβ toxicity is challenged.
Journal ArticleDOI
Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal.
TL;DR: It is shown that PrP is expressed on the surface of several bone marrow cell populations successively enriched in long-term hematopoietic stem cells (HSCs) using flow cytometry analysis and is a marker for HSCs and supports their self-renewal.
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.