title: Gene expression alterations in brains of mice infected with three strains of scrapie.
abstract: BACKGROUND
  Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative disorders which occur in humans and various animal species. Examples include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in deer and elk, and scrapie in sheep, and experimental mice. To gain insights into TSE pathogenesis, we made and used cDNA microarrays to identify disease-associated alterations in gene expression. Brain gene expression in scrapie-infected mice was compared to mock-infected mice at pre-symptomatic and symptomatic time points. Three strains of mouse scrapie that show striking differences in neuropathology were studied: ME7, 22L, and Chandler/RML.
  
  
  RESULTS
  In symptomatic mice, over 400 significant gene expression alterations were identified. In contrast, only 22 genes showed significant alteration in the pre-symptomatic animals. We also identified genes that showed significant differences in alterations in gene expression between strains. Genes identified in this study encode proteins that are involved in many cellular processes including protein folding, endosome/lysosome function, immunity, synapse function, metal ion binding, calcium regulation and cytoskeletal function.
  
  
  CONCLUSIONS
  These studies shed light on the complex molecular events that occur during prion disease, and identify genes whose further study may yield new insights into strain specific neuropathogenesis and ante-mortem tests for TSEs.
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Minnesota, USA. skinn002@umn.edu
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Skinner
authors.forename: Hayet
authors.initials: H
authors.lastname: Abbassi
authors.forename: Bruce
authors.initials: B
authors.lastname: Chesebro
authors.forename: Richard E
authors.initials: RE
authors.lastname: Race
authors.forename: Cavan
authors.initials: C
authors.lastname: Reilly
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012608:Scrapie / Q000235:genetics* / Q000378:metabolism