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Science 29 October 1999:
Vol. 286. no. 5441, pp. 914 - 915
DOI: 10.1126/science.286.5441.914
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Perspectives

NEUROBIOLOGY:
PrP's Double Causes Trouble

Charles Weissmann and Adriano Aguzzi

Various strains of knockout mice--in which the gene that encodes the prion protein (PrP) has been disrupted--have been developed to study how PrP is involved in the prion diseases (which include scrapie, mad cow disease and Creutzfeldt-Jakob disease in humans). However, whereas some strains of PrP knockout mice get sick, others do not. This perplexing observation may now have been solved according to Weissmann and Aguzzi in their Perspective. They discuss a recent paper in the Journal of Molecular Biology that reports the discovery of a new Prnp-like gene called Prnd that may be expressed in the brains of some strains of knockout mice but not in others accounting for the variety in the phenotypes observed.

C. Weissmann is at the MRC Prion Unit/Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1PG, UK. A. Aguzzi is at the Institut für Neuropathologie, Universitätsspital Zürich, 8091 Zürich, Switzerland. E-mail: c.weissmann{at}ic.ac.uk, adriano{at}pathol.unizh.ch

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Dominant-negative Effects of the N-terminal Half of Prion Protein on Neurotoxicity of Prion Protein-like Protein/Doppel in Mice.
D. Yoshikawa, N. Yamaguchi, D. Ishibashi, H. Yamanaka, N. Okimura, Y. Yamaguchi, T. Mori, H. Miyata, K. Shigematsu, S. Katamine, et al. (2008)
J. Biol. Chem. 283, 24202-24211
   Abstract »    Full Text »    PDF »
Physiology of the Prion Protein.
R. Linden, V. R. Martins, M. A. M. Prado, M. Cammarota, I. Izquierdo, and R. R. Brentani (2008)
Physiol Rev 88, 673-728
   Abstract »    Full Text »    PDF »
Truncated Prion Protein and Doppel Are Myelinotoxic in the Absence of Oligodendrocytic PrPC.
I. Radovanovic, N. Braun, O. T. Giger, K. Mertz, G. Miele, M. Prinz, B. Navarro, and A. Aguzzi (2005)
J. Neurosci. 25, 4879-4888
   Abstract »    Full Text »    PDF »
A Pathogenic PrP Mutation and Doppel Interfere with Polarized Sorting of the Prion Protein.
A. Uelhoff, J. Tatzelt, A. Aguzzi, K. F. Winklhofer, and C. Haass (2005)
J. Biol. Chem. 280, 5137-5140
   Abstract »    Full Text »    PDF »
Disruption of Doppel prevents neurodegeneration in mice with extensive Prnp deletions.
N. Genoud, A. Behrens, G. Miele, D. Robay, F. L. Heppner, S. Freigang, and A. Aguzzi (2004)
PNAS 101, 4198-4203
   Abstract »    Full Text »    PDF »
Transgene-driven expression of the Doppel protein in Purkinje cells causes Purkinje cell degeneration and motor impairment.
L. Anderson, D. Rossi, J. Linehan, S. Brandner, and C. Weissmann (2004)
PNAS 101, 3644-3649
   Abstract »    Full Text »    PDF »
Games Played by Rogue Proteins in Prion Disorders and Alzheimer's Disease.
A. Aguzzi and C. Haass (2003)
Science 302, 814-818
   Abstract »    Full Text »    PDF »
Dangerous Liaisons between a Microbe and the Prion Protein.
A. Aguzzi and W.-D. Hardt (2003)
J. Exp. Med. 198, 1-4
   Full Text »    PDF »
PrP knock-out and PrP transgenic mice in prion research.
C Weissmann and E Flechsig (2003)
Br. Med. Bull. 66, 43-60
   Abstract »    Full Text »    PDF »
Production of Mouse ES Cells Homozygous for Cdk5-Phosphorylated Site Mutation in c-src Alleles.
G. Kato and S. Maeda (2003)
J. Biochem. 133, 563-569
   Abstract »    Full Text »    PDF »
The PrP-like Protein Doppel Binds Copper.
K. Qin, J. Coomaraswamy, P. Mastrangelo, Y. Yang, S. Lugowski, C. Petromilli, S. B. Prusiner, P. E. Fraser, J. M. Goldberg, A. Chakrabartty, et al. (2003)
J. Biol. Chem. 278, 8888-8896
   Abstract »    Full Text »    PDF »
Expression of doppel in the CNS of mice does not modulate transmissible spongiform encephalopathy disease.
N. L. Tuzi, E. Gall, D. Melton, and J. C. Manson (2002)
J. Gen. Virol. 83, 705-711
   Abstract »    Full Text »    PDF »
Physiological Expression of the Gene for PrP-Like Protein, PrPLP/Dpl, by Brain Endothelial Cells and its Ectopic Expression in Neurons of PrP-Deficient Mice Ataxic Due to Purkinje Cell Degeneration.
A. Li, S. Sakaguchi, K. Shigematsu, R. Atarashi, B. C. Roy, R. Nakaoke, K. Arima, N. Okimura, J. Kopacek, and S. Katamine (2000)
Am. J. Pathol. 157, 1447-1452
   Abstract »    Full Text »    PDF »
Doppel Is an N-Glycosylated, Glycosylphosphatidylinositol-anchored Protein. EXPRESSION IN TESTIS AND ECTOPIC PRODUCTION IN THE BRAINS OF Prnp0/0 MICE PREDISPOSED TO PURKINJE CELL LOSS.
G. L. Silverman, K. Qin, R. C. Moore, Y. Yang, P. Mastrangelo, P. Tremblay, S. B. Prusiner, F. E. Cohen, and D. Westaway (2000)
J. Biol. Chem. 275, 26834-26841
   Abstract »    Full Text »    PDF »
Cleavage of the Amino Terminus of the Prion Protein by Reactive Oxygen Species.
H. E. M. McMahon, A. Mange, N. Nishida, C. Creminon, D. Casanova, and S. Lehmann (2001)
J. Biol. Chem. 276, 2286-2291
   Abstract »    Full Text »    PDF »
In Vivo Conversion of Cellular Prion Protein to Pathogenic Isoforms, as Monitored by Conformation-specific Antibodies.
T. Yokoyama, K. M. Kimura, Y. Ushiki, S. Yamada, A. Morooka, T. Nakashiba, T. Sassa, and S. Itohara (2001)
J. Biol. Chem. 276, 11265-11271
   Abstract »    Full Text »    PDF »


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