NR AWQN

AU Williams,A.C.; Whatley,S.; Archibald,A.L.; Williams,J.L.

TI Identification of molecular markers of BSE pathogenesis: an investigation of the immune system of BSE infected mice

QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions DIA-60

PT Konferenz-Poster

AB Diagnosis of TSE neuro-degenerative diseases is still based on the detection, at late stages of disease incubation, of the abnormal disease-specific isoform of the host prion protein (PrPsc) accumulated primarily in the central nervous system (CNS) of infected animals. Components of the lymphoreticular system are central to prion pathogenesis and spread to the CNS. Subsequent to infection through either the peripheral or central routes and prior to its appearance in the spinal cord or the CNS, PrPsc usually replicates and accumulates to high levels in the spleen, blood and other lymphoid tissues. In mice PrPsc has been detected in Peyers Patch and spleen within 3 months of BSE infection. This observation gives rise to the possibility of using differential gene expression in peripheral tissues as an early diagnostic test for TSE infection. To support this, work performed at the Roslin Institute identified decreased levels of erythroid differentiation-related factor (EDRF) in the spleen of TSE infected mice and is also reflected in erythroid cells in blood. In the present project gene and protein expression is being investigated in components of the lymphoreticular system to detect genes and/or proteins that are differentially expressed between normal and BSE infected mice (strain 301C, passaged in C57BL sinc s7 s7) during early infection stages. The BXD12ty mouse model used in this investigation is susceptible to both primary and mouse-adapted BSE infection and displays a short incubation period (263±days). Gene expression across the early stages of infectivity, in comparison to age-matched mock-fed controls have been analysed in the spleen and blood cells using Affymetrix GeneChip(R) Mouse Genome 430 2.0 Array. A range of genes have been identified that are differentially expressed in infected animals. SELDI analysis was performed on plasma samples and a number of differentially regulated proteins have been identified. Validation is being carried out by qPCR and Western Blot analysis. Confirmation of these results may lead to diagnostic markers of BSE infection.

AD A.C. Williams, A.L. Archibald, J.L. Williams: Roslin Institute, Genetics and Genomics, Roslin, UK; S. Whatley: Institute of Psychiatry, DeCrespigny Park, London, UK. E-mail: Auriol.wiiliams@bbsrc.ac.uk; John.williams@bbsrc.ac.uk

SP englisch

PO Italien

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