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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PrPC expression and calpain activity independently mediate the effects of closed head injury in mice.
Richard Rubenstein,Kevin K.W. Wang,Allen Chiu,Natalia M. Grin’kina,Deep Raj Sharma,Sanjeev Agarwal,Fan Lin,Zhihui Yang +7 more
TL;DR: Overall, there is SNJ‐1945‐sensitive calpain activation in both neuron and glial cells following CHI, and closed head trauma is not affected by, nor does it have an influence on, PrPC expression, andPrPC expression plays a minor role, if any, in CHI‐induced calpainactivation in vivo.
Journal ArticleDOI
Disease-associated mutations in the prion protein impair laminin-induced process outgrowth and survival.
Cleiton F. Machado,Flavio H. Beraldo,Tiago G. Santos,Dominique Bourgeon,M. C. Landemberger,Martín Roffé,Vilma R. Martins +6 more
TL;DR: Results indicate that PrPC mutations impair process outgrowth and survival mediated by Ln γ1 peptide in neural cells, which may contribute to the pathogenesis of genetic prion diseases.
Journal ArticleDOI
Activation and function of murine primary microglia in the absence of the prion protein.
TL;DR: The role of PrP(C) in mouse primary microglia is investigated, and it is found no differences between wild type and Prnp-null cells in cell morphology or the expression of a microglial marker, and functional roles are - if present - much more subtle than in transformedmicroglial cell lines.
Journal ArticleDOI
Reduced Abundance and Subverted Functions of Proteins in Prion-Like Diseases: Gained Functions Fascinate but Lost Functions Affect Aetiology
TL;DR: This synthesis identifies S OD1 as an exemplar of protein functions being lost during prion-like protein misfolding, because SOD1 is inherently unstable and loses function in its misfolded disease-associated form.
Journal ArticleDOI
Prion protein on astrocytes or in extracellular fluid impedes neurodegeneration induced by truncated prion protein
TL;DR: Results indicated that rescue from neurodegeneration induced by Delta32-134 PrP might involve interactions between neurons expressing truncated PrP and nearby astrocytes expressing WT PrP or extracellular fluid containing solubleWT PrP.
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.