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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Spontaneous Generation of Prion Infectivity in Fatal Familial Insomnia Knockin Mice
Walker S. Jackson,Andrew W. Borkowski,Henryk Faas,Andrew D. Steele,Oliver D. King,Nicki Watson,Alan Jasanoff,Susan Lindquist +7 more
TL;DR: A single amino acid change in PrP is sufficient to induce a distinct neurodegenerative disease and the spontaneous generation of prion infectivity, confirming infectivity did not arise from contaminating agents.
Journal ArticleDOI
Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring
Bruce Chesebro,Brent Race,Kimberly Meade-White,Rachel LaCasse,Richard E. Race,Mikael Klingeborn,James F. Striebel,David W. Dorward,Gillian McGovern,Martin Jeffrey +9 more
TL;DR: Brain graft studies suggested that anchored PrPsen expression was required for gray matter spongiosis during prion infection, and electron and light microscopic studies in infected transgenic mice demonstrated several pathogenic processes not seen in typical prion disease, including cerebral amyloid angiopathy and ultrastructural alterations in perivascular neuropil.
Journal ArticleDOI
The prion protein family: diversity, rivalry, and dysfunction.
TL;DR: Examination of the functional interrelationships of prion proteins has revealed an interesting phenomenon: Doppel is neurotoxic to cerebellar cells in a manner which can be blocked by either PrP(C) or Shadoo, which is expressed in the CNS.
Journal ArticleDOI
Early detection of PrPres in BSE-infected bovine PrP transgenic mice.
Joaquín Castilla,A Gutiérrez Adán,Alejandro Brun,Belén Pintado,Miguel Ángel Ramírez,B. Parra,D. Doyle,Mark Rogers,Francisco J. Salguero,Carlos M. Sánchez,José Manuel Sánchez-Vizcaíno,Juan María Torres +11 more
TL;DR: The result indicates that prion infectivity in experimental mouse bioassays can be measured earlier by assessing immunologically the presence of PrPres in brains from inoculated animals.
Journal ArticleDOI
Cellular prion protein expression in astrocytes modulates neuronal survival and differentiation.
Flavia Regina Souza Lima,Camila P. Arantes,Angelita G. Muras,Regina Nomizo,Ricardo R. Brentani,Vilma R. Martins +5 more
TL;DR: Data indicate that PrPC expression in astrocytes is critical for sustaining cell‐to‐cell interactions, the organization of the extracellular matrix, and the secretion of soluble factors, all of which are essential events for neuronal differentiation and survival.
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.