NR ATKO
AU Williams,A.C.; Williams,J.L.; Whatley,S.
TI Identification of molecular markers of BSE pathogenesis: An investigation of the immune system of BSE infected mice.
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Diagnosis DIA-26
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.
Gene expression, during early infection is being investigated in both the spleen and white blood cells to detect genes that are differentially expressed between normal and BSE infected mice (strain 301C, passaged in C57BL sinc s7 s7). 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 stages of infectivity, in comparison to age-matched mock-fed controls have been analysed in the spleen using Affymetrix GeneChip(R) Mouse Genome 430 2.0 Array and a range of genes have been identified that are differentially expressed in infected animals. Validation of these results is being carried out by qPCR and it is hoped that this may lead to a diagnostic marker.
AD A.C.Williams, J.L.Williams, Roslin Institute, Roslin, Midlothian, EH25 9PS; S.Whatley, Institute of Psychiatry, DeCrespigny Park, London, SE5 8AF
SP englisch
PO Deutschland