Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 14 December 1990:
Vol. 250. no. 4987, pp. 1587 - 1590
DOI: 10.1126/science.1980379
Prev | Table of Contents | Next

Articles

Science, Vol 250, Issue 4987, 1587-1590
Copyright © 1990 by American Association for the Advancement of Science

articles

Spontaneous neurodegeneration in transgenic mice with mutant prion protein

KK Hsiao, M Scott, D Foster, DF Groth, SJ DeArmond, and SB Prusiner

Department of Neurology, University of California, San Francisco 94143.

Transgenic mice were created to assess genetic linkage between Gerstmann-Straussler-Scheinker syndrome and a leucine substitution at codon 102 of the human prion protein gene. Spontaneous neurologic disease with spongiform degeneration and gliosis similar to that in mouse scrapie developed at a mean age of 166 days in 35 mice expressing mouse prion protein with the leucine substitution. Thus, many of the clinical and pathological features of Gerstmann-Straussler-Scheinker syndrome are reproduced in transgenic mice containing a prion protein with a single amino acid substitution, illustrating that a neurodegenerative process similar to a human disease can be genetically modeled in animals.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Design and construction of diverse mammalian prion strains.
D. W. Colby, K. Giles, G. Legname, H. Wille, I. V. Baskakov, S. J. DeArmond, and S. B. Prusiner (2009)
PNAS 106, 20417-20422
   Abstract »    Full Text »    PDF »
A New Transgenic Mouse Model of Gerstmann-Straussler-Scheinker Syndrome Caused by the A117V Mutation of PRNP.
W. Yang, J. Cook, B. Rassbach, A. Lemus, S. J. DeArmond, and J. A. Mastrianni (2009)
J. Neurosci. 29, 10072-10080
   Abstract »    Full Text »    PDF »
Phosphorylation of Prion Protein at Serine 43 Induces Prion Protein Conformational Change.
P. N. Giannopoulos, C. Robertson, J. Jodoin, H. Paudel, S. A. Booth, and A. C. LeBlanc (2009)
J. Neurosci. 29, 8743-8751
   Abstract »    Full Text »    PDF »
Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins.
E. A. Asante, I. Gowland, A. Grimshaw, J. M. Linehan, M. Smidak, R. Houghton, O. Osiguwa, A. Tomlinson, S. Joiner, S. Brandner, et al. (2009)
J. Gen. Virol. 90, 546-558
   Abstract »    Full Text »    PDF »
Constraining the loop, releasing prion infectivity.
C. Soto (2009)
PNAS 106, 10-11
   Full Text »    PDF »
De novo generation of a transmissible spongiform encephalopathy by mouse transgenesis.
C. J. Sigurdson, K. P. R. Nilsson, S. Hornemann, M. Heikenwalder, G. Manco, P. Schwarz, D. Ott, T. Rulicke, P. P. Liberski, C. Julius, et al. (2009)
PNAS 106, 304-309
   Abstract »    Full Text »    PDF »
Molecular and Transmission Characteristics of Primary-Passaged Ovine Scrapie Isolates in Conventional and Ovine PrP Transgenic Mice.
A. M. Thackray, L. Hopkins, J. Spiropoulos, and R. Bujdoso (2008)
J. Virol. 82, 11197-11207
   Abstract »    Full Text »    PDF »
A General Model of Prion Strains and Their Pathogenicity.
J. Collinge and A. R. Clarke (2007)
Science 318, 930-936
   Abstract »    Full Text »    PDF »
Mad Fly Disease.
J. Chandran and P. Lewis (2007)
J. Neurosci. 27, 971-972
   Full Text »    PDF »
Accelerated Accumulation of Misfolded Prion Protein and Spongiform Degeneration in a Drosophila Model of Gerstmann-Straussler-Scheinker Syndrome.
B. A. Gavin, M. J. Dolph, N. R. Deleault, J. C. Geoghegan, V. Khurana, M. B. Feany, P. J. Dolph, and S. Supattapone (2006)
J. Neurosci. 26, 12408-12414
   Abstract »    Full Text »    PDF »
A systematic review of prion therapeutics in experimental models.
C. R Trevitt and J. Collinge (2006)
Brain 129, 2241-2265
   Abstract »    Full Text »    PDF »
Prion clearance in bigenic mice.
J. G. Safar, S. J. DeArmond, K. Kociuba, C. Deering, S. Didorenko, E. Bouzamondo-Bernstein, S. B. Prusiner, and P. Tremblay (2005)
J. Gen. Virol. 86, 2913-2923
   Abstract »    Full Text »    PDF »
A case-control study of sporadic Creutzfeldt-Jakob disease in the United Kingdom: Analysis of clustering.
L. Linsell, S. N. Cousens, P. G. Smith, R. S.G. Knight, M. Zeidler, G. Stewart, R. de Silva, T. F.G. Esmonde, H. J.T. Ward, and R. G. Will (2004)
Neurology 63, 2077-2083
   Abstract »    Full Text »    PDF »
Mutant PrPSc Conformers Induced by a Synthetic Peptide and Several Prion Strains.
P. Tremblay, H. L. Ball, K. Kaneko, D. Groth, R. S. Hegde, F. E. Cohen, S. J. DeArmond, S. B. Prusiner, and J. G. Safar (2004)
J. Virol. 78, 2088-2099
   Abstract »    Full Text »    PDF »
Subclinical Prion Disease Induced by Oral Inoculation.
A. M. Thackray, M. A. Klein, and R. Bujdoso (2003)
J. Virol. 77, 7991-7998
   Abstract »    Full Text »    PDF »
Molecular Distinction between Pathogenic and Infectious Properties of the Prion Protein.
R. Chiesa, P. Piccardo, E. Quaglio, B. Drisaldi, S. L. Si-Hoe, M. Takao, B. Ghetti, and D. A. Harris (2003)
J. Virol. 77, 7611-7622
   Abstract »    Full Text »    PDF »
Atypical Effect of Salts on the Thermodynamic Stability of Human Prion Protein.
A. C. Apetri and W. K. Surewicz (2003)
J. Biol. Chem. 278, 22187-22192
   Abstract »    Full Text »    PDF »
Introduction to the transmissible spongiform encephalopathies or prion diseases.
B. Chesebro (2003)
Br. Med. Bull. 66, 1-20
   Abstract »    Full Text »    PDF »
Ethical issues in human prion diseases.
S. Tabrizi, C. Elliott, and C Weissmann (2003)
Br. Med. Bull. 66, 305-316
   Abstract »    Full Text »    PDF »
Chronic Subclinical Prion Disease Induced by Low-Dose Inoculum.
A. M. Thackray, M. A. Klein, A. Aguzzi, and R. Bujdoso (2002)
J. Virol. 76, 2510-2517
   Abstract »    Full Text »    PDF »
Cellular Phenotyping of Secretory and Nuclear Prion Proteins Associated with Inherited Prion Diseases.
H. Lorenz, O. Windl, and H. A. Kretzschmar (2002)
J. Biol. Chem. 277, 8508-8516
   Abstract »    Full Text »    PDF »
Is there evidence for exogenous risk factors in the aetiology and spread of Creutzfeldt-Jakob disease?.
C. E. M. Hillier and R. L. Salmon (2000)
QJM 93, 617-631
   Full Text »    PDF »
Species-barrier-independent prion replication in apparently resistant species.
A. F. Hill, S. Joiner, J. Linehan, M. Desbruslais, P. L. Lantos, and J. Collinge (2000)
PNAS 97, 10248-10253
   Abstract »    Full Text »    PDF »
Accumulation of protease-resistant prion protein (PrP) and apoptosis of cerebellar granule cells in transgenic mice expressing a PrP insertional mutation.
R. Chiesa, B. Drisaldi, E. Quaglio, A. Migheli, P. Piccardo, B. Ghetti, and D. A. Harris (2000)
PNAS 97, 5574-5579
   Abstract »    Full Text »    PDF »
Prions in Saccharomyces and Podospora spp.: Protein-Based Inheritance.
R. B. Wickner, K. L. Taylor, H. K. Edskes, M.-L. Maddelein, H. Moriyama, and B. T. Roberts (1999)
Microbiol. Mol. Biol. Rev. 63, 844-861
   Abstract »    Full Text »    PDF »
Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene.
G. R. Mallucci, T. A. Campbell, A. Dickinson, J. Beck, M. Holt, G. Plant, K. W. de Pauw, R. N. Hakin, C. E. Clarke, S. Howell, et al. (1999)
Brain 122, 1823-1837
   Abstract »    Full Text »    PDF »
Involvement of the spinal posterior horn in Gerstmann-Straussler-Scheinker disease (PrP P102L).
M. Yamada, H. Tomimitsu, T. Yokota, H. Tomi, N. Sunohara, M. Mukoyama, Y. Itoh, N. Suematsu, E. Otomo, R. Okeda, et al. (1999)
Neurology 52, 260
   Abstract »    Full Text »
1755 and all that: a historical primer of transmissible spongiform encephalopathy.
P. Brown and R. Bradley (1998)
BMJ 317, 1688-1692
   Full Text »
Prions.
S. B. Prusiner (1998)
PNAS 95, 13363-13383
   Abstract »    Full Text »    PDF »
Genetic Classification of Primary Neurodegenerative Disease.
J. Hardy and K. Gwinn-Hardy (1998)
Science 282, 1075-1079
   Abstract »    Full Text »
A Transmembrane Form of the Prion Protein in Neurodegenerative Disease.
R. S. Hegde, J. A. Mastrianni, M. R. Scott, K. A. DeFea, P. Tremblay, M. Torchia, S. J. DeArmond, S. B. Prusiner, and V. R. Lingappa (1998)
Science 279, 827-834
   Abstract »    Full Text »
The prion model for [URE3] of yeast: Spontaneous generation and requirements for propagation.
D. C. Masison, M.-L. Maddelein, and R. B. Wickner (1997)
PNAS 94, 12503-12508
   Abstract »    Full Text »    PDF »
Prion Diseases and the BSE Crisis.
S. B. Prusiner (1997)
Science 278, 245-251
   Abstract »    Full Text »
Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion propagation.
K. Kaneko, L. Zulianello, M. Scott, C. M. Cooper, A. C. Wallace, T. L. James, F. E. Cohen, and S. B. Prusiner (1997)
PNAS 94, 10069-10074
   Abstract »    Full Text »    PDF »
Recombinant scrapie-like prion protein of 106 amino acids is soluble.
T. Muramoto, M. Scott, F. E. Cohen, and S. B. Prusiner (1996)
PNAS 93, 15457-15462
   Abstract »    Full Text »    PDF »
Interactions between wild-type and mutant prion proteins modulate neurodegeneration in transgenic mice..
G C Telling, T Haga, M Torchia, P Tremblay, S J DeArmond, and S B Prusiner (1996)
Genes & Dev. 10, 1736-1750
   Abstract »    PDF »
Molecular Biology and Genetics of Prion Diseases.
S.B. Prusiner (1996)
Cold Spring Harb Symp Quant Biol 61, 473-493
   Abstract »    PDF »
Prion Protein Structure and Scrapie Replication: Theoretical, Spectroscopic, and Genetic Investigations.
P. Bamborough, H. Wille, G.C. Telling, F. Yehiely, S.B. Prusiner, and F.E. Cohen (1996)
Cold Spring Harb Symp Quant Biol 61, 495-509
   Abstract »    PDF »
The Role of PrP in Pathogenesis of Experimental Scrapie.
C. Weissmann, M. Fischer, A. Raeber, H. Bueler, A. Sailer, D. Shmerling, T. Rulicke, S. Brandner, and A. Aguzzi (1996)
Cold Spring Harb Symp Quant Biol 61, 511-522
   Abstract »    PDF »
Prions of Yeast, [PSI] and [URE3], as Models for Neurodegenerative Diseases.
R.B. Wickner, D.C. Masison, H.K. Edskes, and M.-L. Maddelein (1996)
Cold Spring Harb Symp Quant Biol 61, 541-550
   Abstract »    PDF »
Transgenic mice: What are we learning about gene function and neurological disease?.
F. M. Longo (1995)
Neuroscientist 1, 309-311
   PDF »
A Mutant Prion Protein Displays an Aberrant Membrane Association When Expressed in Cultured Cells.
S. Lehmann and D. A. Harris (1995)
J. Biol. Chem. 270, 24589-24597
   Abstract »    Full Text »    PDF »
Prion Protein Isoforms, a Convergence of Biological and Structural Investigations.
M. A. Baldwin, F. E. Cohen, and S. B. Prusiner (1995)
J. Biol. Chem. 270, 19197-19200
   Full Text »    PDF »
Structural clues to prion replication.
F. Cohen, K. Pan, Z Huang, M Baldwin, R. Fletterick, and S. Prusiner (1994)
Science 264, 530-531
   PDF »
Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie..
D Westaway, V Zuliani, C M Cooper, M Da Costa, S Neuman, A L Jenny, L Detwiler, and S B Prusiner (1994)
Genes & Dev. 8, 959-969
   Abstract »    PDF »
Genetic and Infectious Prion Diseases.
S. B. Prusiner (1993)
Arch Neurol 50, 1129-1153
   Abstract »    PDF »
Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters..
R Hecker, A Taraboulos, M Scott, K M Pan, S L Yang, M Torchia, K Jendroska, S J DeArmond, and S B Prusiner (1992)
Genes & Dev. 6, 1213-1228
   Abstract »    PDF »
Molecular biology of prion diseases.
S. Prusiner (1991)
Science 252, 1515-1522
   Abstract »    PDF »
Prion proposal proved?.
J Marx (1991)
Science 251, 1022-1023
   PDF »
A POSSIBLE MOLECULAR CAUSE OF TWO NEURODEGENERATIVE DISEASES.
(1991)
Journal Watch (General) 1991, 8
   Full Text »
Human brain disease recreated in mice.
J Marx (1990)
Science 250, 1509-1510
   PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)