This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xiang, W.
Right arrow Articles by Kretzschmar, H. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xiang, W.
Right arrow Articles by Kretzschmar, H. A.

 Previous Article  |  Next Article 

Journal of Virology, October 2004, p. 11051-11060, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11051-11060.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Identification of Differentially Expressed Genes in Scrapie-Infected Mouse Brains by Using Global Gene Expression Technology

Wei Xiang,1 Otto Windl,1,{dagger} Gerda Wünsch,1 Martin Dugas,2 Alexander Kohlmann,3 Nicola Dierkes,1 Ingo M. Westner,1 and Hans A. Kretzschmar1*

Institute of Neuropathology,1 Department of Medical Informatics, Biometrics, and Epidemiology,2 Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany3

Received 6 February 2004/ Accepted 14 June 2004

The pathogenesis of prion diseases, a class of transmissible fatal neurodegenerative diseases in humans and animals, is still unclear. The aim of this study was to identify the differentially regulated genes that correlate with the development of prion diseases for a better understanding of their pathological mechanisms. We employed Affymetrix Mouse Expression Arrays 430A containing >22,000 transcripts and compared the global gene expression profiles from brains of mice who were intracerebrally inoculated with scrapie strains ME7 and RML with those from brains of uninfected and mock-infected mice. The microarray data were analyzed by Significance Analysis of Microarrays, revealing 121 genes whose expression increased at least twofold in both ME7- and RML-infected mouse brains, with an estimated false discovery rate of ≤5%. These genes encode proteins involved in proteolysis, protease inhibition, cell growth and maintenance, the immune response, signal transduction, cell adhesion, and molecular metabolism. The time course of expression generally showed up-regulation of these genes from 120 days postinoculation (dpi) for ME7-inoculated mouse brains and from 90 dpi for RML-inoculated mouse brains. The onset of elevated expression correlated temporally with the onset of PrPSc accumulation and the activation of glia, which may have contributed to neuronal cell death. Among the differentially regulated genes reported in the present study, the emergence of genes for several cathepsins and S100 calcium binding proteins was conspicuous. These and other genes reported here may represent novel potential diagnostic and therapeutic targets for prion disease.

* Corresponding author. Mailing address: Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Feodor-Lynen-Strasse 23, D-81377 Munich, Germany. Phone: 49-89-2180-78000. Fax: 49-89-2180-78037. E-mail: Hans.Kretzschmar{at}med.uni-muenchen.de.

{dagger} Present address: Veterinary Laboratories Agency, Weybridge, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom.

Journal of Virology, October 2004, p. 11051-11060, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11051-11060.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Guillerme-Bosselut, F., Forestier, L., Jayat-Vignoles, C., Vilotte, J.-L., Popa, I., Portoukalian, J., Le Dur, A., Laude, H., Julien, R., Gallet, P.-F. (2009). Glycosylation-related gene expression profiling in the brain and spleen of scrapie-affected mouse. Glycobiology 19: 879-889 [Abstract] [Full Text]  
  • Riemer, C., Schultz, J., Burwinkel, M., Schwarz, A., Mok, S. W. F., Gultner, S., Bamme, T., Norley, S., van Landeghem, F., Lu, B., Gerard, C., Baier, M. (2008). Accelerated Prion Replication in, but Prolonged Survival Times of, Prion-Infected CXCR3-/- Mice. J. Virol. 82: 12464-12471 [Abstract] [Full Text]  
  • Kumar, R., McClain, D., Young, R., Carlson, G. A. (2008). Cholesterol transporter ATP-binding cassette A1 (ABCA1) is elevated in prion disease and affects PrPC and PrPSc concentrations in cultured cells. J. Gen. Virol. 89: 1525-1532 [Abstract] [Full Text]  
  • Haviv, Y., Avrahami, D., Ovadia, H., Ben-Hur, T., Gabizon, R., Sharon, R. (2008). Induced Neuroprotection Independently From PrPSc Accumulation in a Mouse Model for Prion Disease Treated With Simvastatin. Arch Neurol 65: 762-775 [Abstract] [Full Text]  
  • Kercher, L., Favara, C., Striebel, J. F., LaCasse, R., Chesebro, B. (2007). Prion Protein Expression Differences in Microglia and Astroglia Influence Scrapie-Induced Neurodegeneration in the Retina and Brain of Transgenic Mice. J. Virol. 81: 10340-10351 [Abstract] [Full Text]  
  • Friedman-Levi, Y., Ovadia, H., Hoftberger, R., Einstein, O., Abramsky, O., Budka, H., Gabizon, R. (2007). Fatal Neurological Disease in Scrapie-Infected Mice Induced for Experimental Autoimmune Encephalomyelitis. J. Virol. 81: 9942-9949 [Abstract] [Full Text]  
  • Sawiris, G. P., Becker, K. G., Elliott, E. J., Moulden, R., Rohwer, R. G. (2007). Molecular analysis of bovine spongiform encephalopathy infection by cDNA arrays. J. Gen. Virol. 88: 1356-1362 [Abstract] [Full Text]  
  • Piening, N., Nonno, R., Di Bari, M., Walter, S., Windl, O., Agrimi, U., Kretzschmar, H. A., Bertsch, U. (2006). Conversion Efficiency of Bank Vole Prion Protein in Vitro Is Determined by Residues 155 and 170, but Does Not Correlate with the High Susceptibility of Bank Voles to Sheep Scrapie in Vivo. J. Biol. Chem. 281: 9373-9384 [Abstract] [Full Text]  
  • Paulus, C., Sollars, P. J., Pickard, G. E., Enquist, L. W. (2006). Transcriptome Signature of Virulent and Attenuated Pseudorabies Virus-Infected Rodent Brain. J. Virol. 80: 1773-1786 [Abstract] [Full Text]  
  • Windl, O., Buchholz, M., Neubauer, A., Schulz-Schaeffer, W., Groschup, M., Walter, S., Arendt, S., Neumann, M., Voss, A. K., Kretzschmar, H. A. (2005). Breaking an Absolute Species Barrier: Transgenic Mice Expressing the Mink PrP Gene Are Susceptible to Transmissible Mink Encephalopathy. J. Virol. 79: 14971-14975 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»