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PMID: 8635458 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie.

The EMBO journal ·Vol. 15 ·No. 6 ·1996-03-15 ·Pages 1255-64

Fischer M, Rülicke T, Raeber A, Sailer A, Moser M, Oesch B, Brandner S, Aguzzi A, Weissmann C

Abstract

The 'protein only' hypothesis postulates that the prion, the agent causing transmissible spongiform encephalopathies, is PrP(Sc), an isoform of the host protein PrP(C). Protease treatment of prion preparations cleaves off approximately 60 N-terminal residues of PrP(Sc) but does not abrogate infectivity. Disruption of the PrP gene in the mouse abolishes susceptibility to scrapie and prion replication. We have introduced into PrP knockout mice transgenes encoding wild-type PrP or PrP lacking 26 or 49 amino-proximal amino acids which are protease susceptible in PrP(Sc). Inoculation with prions led to fatal disease, prion propagation and accumulation of PrP(Sc) in mice expressing both wild-type and truncated PrPs. Within the framework of the 'protein only' hypothesis, this means that the amino-proximal segment of PrP(C) is not required either for its susceptibility to conversion into the pathogenic, infectious form of PrP or for the generation of PrP(Sc).

MeSH Terms
Amino Acid Sequence Amyloid/deficiency,genetics Animals Base Sequence Brain/anatomy & histology Disease Susceptibility Mice Mice, Knockout Molecular Sequence Data Mutation Nerve Tissue Proteins/biosynthesis,genetics PrPC Proteins/genetics PrPSc Proteins/biosynthesis,genetics Prion Proteins Prions/biosynthesis,genetics Protein Precursors/deficiency,genetics RNA, Messenger/isolation & purification Scrapie/etiology,genetics,transmission Sequence Deletion
Chemicals
Amyloid Nerve Tissue Proteins PrPC Proteins PrPSc Proteins Prion Proteins Prions Prnp protein, mouse Protein Precursors RNA, Messenger
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Fischer M
Institut für Molekularbiologie der Universität Zürich, Switzerland.
Rülicke T
Raeber A
Sailer A
Moser M
Oesch B
Brandner S
Aguzzi A
Weissmann C
References (50)
50 references, click to expand
  1. High prion and PrPSc levels but delayed onset of disease in scrapie-inoculated mice heterozygous for a disrupted PrP gene.
    Mol Med. 1994 Nov;1(1):19-30 PMID: 8790598
  2. Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins.
    Cell. 1994 Jan 14;76(1):117-29 PMID: 8287472
  3. Self-replication and scrapie.
    Nature. 1967 Sep 2;215(5105):1043-4 PMID: 4964084
  4. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  5. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes.
    Cell. 1980 May;20(1):95-105 PMID: 6893015
  6. Measurement of the scrapie agent using an incubation time interval assay.
    Ann Neurol. 1982 Apr;11(4):353-8 PMID: 6808890
  7. Identification of a protein that purifies with the scrapie prion.
    Science. 1982 Dec 24;218(4579):1309-11 PMID: 6815801
  8. A protease-resistant protein is a structural component of the scrapie prion.
    Cell. 1983 Nov;35(1):57-62 PMID: 6414721
  9. Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs.
    Proc Natl Acad Sci U S A. 1985 Jul;82(13):4438-42 PMID: 3892534
  10. Scrapie and cellular prion proteins share polypeptide epitopes.
    J Infect Dis. 1986 May;153(5):848-54 PMID: 2422294
  11. Separation and properties of cellular and scrapie prion proteins.
    Proc Natl Acad Sci U S A. 1986 Apr;83(8):2310-4 PMID: 3085093
  12. Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene.
    Cell. 1986 Aug 1;46(3):417-28 PMID: 2873895
  13. Evidence suggesting that PrP is not the infectious agent in Creutzfeldt-Jakob disease.
    EMBO J. 1987 Feb;6(2):341-7 PMID: 3556164
  14. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  15. Introns increase transcriptional efficiency in transgenic mice.
    Proc Natl Acad Sci U S A. 1988 Feb;85(3):836-40 PMID: 3422466
  16. Molecular pathology of scrapie-associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie.
    Eur J Biochem. 1988 Mar 1;172(2):271-7 PMID: 2894984
  17. Genetic aspects of unconventional virus infections: the basis of the virino hypothesis.
    Ciba Found Symp. 1988;135:63-83 PMID: 3044709
  18. Immunoaffinity purification and neutralization of scrapie prion infectivity.
    Proc Natl Acad Sci U S A. 1988 Sep;85(18):6617-21 PMID: 3137571
  19. Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.
    Mol Cell Biol. 1988 Dec;8(12):5528-40 PMID: 3149717
  20. Post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy.
    J Virol Methods. 1989 Apr-May;24(1-2):215-21 PMID: 2569471
  21. Transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques.
    Cell. 1989 Dec 1;59(5):847-57 PMID: 2574076
  22. Rapid detection of Creutzfeldt-Jakob disease and scrapie prion proteins.
    Neurology. 1990 Jan;40(1):110-7 PMID: 1967489
  23. Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication.
    Cell. 1990 Nov 16;63(4):673-86 PMID: 1977523
  24. Protease sensitivity and nuclease resistance of the scrapie agent propagated in vitro in neuroblastoma cells.
    J Virol. 1991 Feb;65(2):1031-4 PMID: 1846182
  25. Spontaneous neurodegeneration in transgenic mice with mutant prion protein.
    Science. 1990 Dec 14;250(4987):1587-90 PMID: 1980379
  26. Spongiform encephalopathies. The prion's progress.
    Nature. 1991 Feb 14;349(6310):569-71 PMID: 2000133
  27. Tissue-specific expression of p53 in transgenic mice is regulated by intron sequences.
    Mol Carcinog. 1991;4(1):3-9 PMID: 1848986
  28. Molecular biology of prion diseases.
    Science. 1991 Jun 14;252(5012):1515-22 PMID: 1675487
  29. Paradoxical shortening of scrapie incubation times by expression of prion protein transgenes derived from long incubation period mice.
    Neuron. 1991 Jul;7(1):59-68 PMID: 1676894
  30. Secondary structure analysis of the scrapie-associated protein PrP 27-30 in water by infrared spectroscopy.
    Biochemistry. 1991 Aug 6;30(31):7672-80 PMID: 1678278
  31. Simplified mammalian DNA isolation procedure.
    Nucleic Acids Res. 1991 Aug 11;19(15):4293 PMID: 1870982
  32. Genetic manipulation of mammals and its application in reproductive biology.
    J Reprod Fertil. 1991 Jul;92(2):245-79 PMID: 1886087
  33. Copurification of Sp33-37 and scrapie agent from hamster brain prior to detectable histopathology and clinical disease.
    J Gen Virol. 1991 Dec;72 ( Pt 12):2905-13 PMID: 1684986
  34. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein.
    Nature. 1992 Apr 16;356(6370):577-82 PMID: 1373228
  35. Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation.
    Nature. 1992 Apr 16;356(6370):598-601 PMID: 1348570
  36. Structure and polymorphism of the mouse prion protein gene.
    Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6418-22 PMID: 7912827
  37. The nature of the scrapie agent: the virus theory.
    Ann N Y Acad Sci. 1994 Jun 6;724:246-58 PMID: 8030946
  38. Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.
    Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9126-30 PMID: 7916462
  39. Amyloid fibrils in Gerstmann-Sträussler-Scheinker disease (Indiana and Swedish kindreds) express only PrP peptides encoded by the mutant allele.
    Cell. 1994 Nov 18;79(4):695-703 PMID: 7954833
  40. Prions and related neurological diseases.
    Mol Aspects Med. 1994;15(3):195-291 PMID: 7968312
  41. Developmental expression of the prion protein gene in glial cells.
    Neuron. 1995 Mar;14(3):509-17 PMID: 7695897
  42. Transmission of fatal familial insomnia to laboratory animals.
    Lancet. 1995 Aug 26;346(8974):569-70 PMID: 7658786
  43. Normal host prion protein necessary for scrapie-induced neurotoxicity.
    Nature. 1996 Jan 25;379(6563):339-43 PMID: 8552188
  44. Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing.
    Biochemistry. 1993 Mar 2;32(8):1991-2002 PMID: 8448158
  45. Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3182-6 PMID: 8475059
  46. An amber mutation of prion protein in Gerstmann-Sträussler syndrome with mutant PrP plaques.
    Biochem Biophys Res Commun. 1993 Apr 30;192(2):525-31 PMID: 8097911
  47. Mice devoid of PrP are resistant to scrapie.
    Cell. 1993 Jul 2;73(7):1339-47 PMID: 8100741
  48. Analysis of nucleic acids in purified scrapie prion preparations.
    Arch Virol Suppl. 1993;7:215-25 PMID: 8219805
  49. Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.
    Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10962-6 PMID: 7902575
  50. No propagation of prions in mice devoid of PrP.
    Cell. 1994 Jul 1;77(7):967-8 PMID: 7912659
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-03-15
Pages
1255-64
Language
English
Region
England
NLM ID
8208664
PMCID
PMC450028
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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