NR AXIP
AU Banner,S.J.; Brown,D.; Thomson,V.; Shillinglaw,S.; Clarke,A.R.; Manson,J.; Gill,A.C.
TI Analysis of Murine CNS Proteomes from PRP0/0, PRPP101LL, PRPG3 and WT Mice
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.02
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB The prion protein (PrP) is fundamental to TSE disease biology and its conversion from the normal, cellular form (PrPc) to a detergent insoluble, protease resistant isoform (PrPsc) appears to be a pre-requisite for disease progression. Aggregates that accumulate in TSE disease are strongly immunopositive for PrPsc leading to the suggestion that PrPsc aggregation may be responsible for neurodegeneration via a 'gain of function' mechanism. However, in some TSE cases, extensive pathology can exist in the absence of detectable levels of PrPsc. The role of PrPsc in neuropathogenesis is therefore unclear and an alternate hypothesis suggests that the loss of PrPc function during disease progression could be responsible for neurodegeneration. We hypothesise that PrPc may function as a neuroprotective molecule and believe that mutations in the PrnP gene could initiate pathological disease due to impaired functioning of PrPc. The normal biological role of PrPc is still unclear and mice devoid of PrPc (PrP0/0) were developed in order to address this point. These mice show subtle defects in synaptic transmission, mitochondrial function and circadian rhythm and an initial, collaborative, microarray based pilot study of wildtype (WT) versus PrP0/0 mice uncovered several intriguing differences between them. Our work intends to confirm and build on this preliminary microarray data and aims to define more specifically the temporal molecular changes in PrP0/0 mice and establish whether mutant PrP, with a reduced neuroprotective function, can invoke similar changes. Here we present data generated from the comparative proteomic analysis of mouse CNS tissue from WT, PrP0/0, PrP101LL & PrPG3 mice at 400 and/or 700days of age. Soluble mouse brain proteins have been subjected to isoelectric focusing, separated by SDS PAGE and then silver stained. Gel images have been digitised and comparative analyses have been performed using Progenesis SameSpots analysis software. Using this approach we have identified several protein changes occurring in WT and PrP0/0 brain tissue from 700day old mice. Furthermore, we have expanded the study and begun to characterise the changes in protein expression that occur at 400days in transgenic mice that posses mutant PrP molecules (P101L and G3) as well as in WT and PrP0/0 mice. Ultimately, we hope to gain an insight into the influence that PrPc can have in normal cellular function and begin to define a role for PrPc in neuroprotection during ageing.
AD S.J. Banner, D. Brown, V. Thomson, S. Shillinglaw, J. Manson, A.C. Gill, Roslin Institute (Edinburgh), UK; A.R. Clarke, Cardiff University, Biomedical Sciences Building, UK
SP englisch
PO Schottland
EA pdf-Datei und Poster (Autorenliste um V. Thomson reduziert)