NR AXHW
AU Alejo Blanco,A.R.; Brown,A.R.; Brakhfoguel,I.; Moore,R.; Smith,R.; Brown,K.; Fazakerley,J.; Mabbott,N.; Manson,J.C.; Clinton,M.
TI Does the Erythroid Lineage have a Role in Prion Disease?
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.25
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: For many prion diseases there is an obligate expansion and dissemination of infectious material within the lymphoreticular system and particularly within the spleen. Although it is well established that blood can carry infectivity, there is confusion over which of the haematopoietic lineages can potentially harbour, transport and propagate the infectious agent. Our previous studies, identified a dramatic TSE-associated decrease in the expression of an erythroid-specific transcript, termed erythroid-associated factor (ERAF). This finding suggested a previously unrecognized role for cells of the erythroid lineage in the peripheral pathogenesis of TSEs.
Aims: We have undertaken both transcriptomic and proteomic approaches to further investigate the involvement of haematopoietic tissues in TSE diseases.
Methods: We have extended our original findings on the effect of TSEs on the erythroid lineage. Firstly, we measured the expression of a number of erythroid-specific transcripts in haematopoietic tissues of Control and Infected animals to determine whether ERAF was the only erythroid transcript affected. As a second approach, we compared protein expression patterns between control and infected samples. This approach has enabled us to compare the profiles of over 3000 proteins found in haematopoietic tissues.
Results: We report that the dramatic down regulation of several functionally-diverse erythroid genes is a common feature of all scrapie-infected mice studied. In contrast, expression of the same genes is largely unaltered in five virus models, with parallels to TSE pathogenesis. In addition we have identified a further 25 proteins from haematopoietic tissue which show differential expression as a result of infection. The simplest explanation for this overall loss in erythroid expression is due to the loss of a cell type and flow cytometry has identified a precursor erythroid lineage that is decreased during prion infection.
Conclusion: Our data suggests that a number of different cellular processes are affected in the blood of infected animals. These findings suggest that a degree of "global down regulation" of erythroid gene expression is a consistent feature of murine scrapie. This loss of erythroid function is accompanied by a decrease in an erythroid precursor cell population. A prion disease-associated profile of erythroid gene/protein expression may prove a useful indicator for disease in peripheral tissue.
AD R. Alejo Blanco, A. Brown, I. Brakhfoguel, R. Smith, M. Clinton, Roslin Institute, Gene Function and Development, UK; R. Moore, Roslin Institute, Genetics and Genomics, UK; K. Brown, N. Mabbott, J. Manson, Roslin Institute, Neuropathogenesis Unit, UK; J. Fazakerley, University of Edinburgh, Centre for Infectious Diseases, UK
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: Scrapie and the erythroid lineage)