Early Host Responses to Prion Infection: Development of In Vivo and In Vitro Assays
Annual rept. 1 May 2004-30 Apr 2005
MCLAUGHLIN RESEARCH INST GREAT FALLS MT
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The first goal is to identify changes in mRNA in blood cells and in serum glycoprotein concentrations that are induced by prion infection in mice. Using a panel of mouse strains and genetically modified mice inoculated with two different prion strains we have found 57 genes that are differentially expressed in the brains of four host-agent combinations. Hundreds of genes are differentially expressed in any single host-agent combination, illustrating the power of analyzing multiple combinations. Some of these genes are differentially expressed as early as 4 weeks post-inoculation, well before signs of neurological disease are apparent, making them candidates for early diagnostic markers. One of these early genes is differentially expressed in blood cells. Application of a novel mass spectrometry-based proteomics technology is underway to identify quantitative changes in serum glycoproteins resulting from prion infection. The second goal is to determine whether CNS stem cells can provide an in vitro model for prion infection. We have successfully infected cell lines from transgenic and non-transgenic mice with scrapie prions, providing the ability to analyze the genetics of prion susceptibility in cell culture. These results also offer the possibility of an in vitro bioassay for prions.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research
- Anatomy and Physiology