NR AWBF
AU Asante,E.A.; Linehan,J.M.; Gowland,I.; Joiner,S.; Fox,K.; Cooper,S.; Osiguwa,O.; Gorry,M.; Welch,J.; Houghton,R.; Desbruslais,M.; Brandner,S.; Wadsworth,J.D.F.; Collinge,J.
TI Dissociation of pathological and molecular phenotype of vCJD in transgenic human PrP 129 heterozygous 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 PR-02
PT Konferenz-Poster
AB All neuropathologically confirmed cases of variant Creutzfeldt-Jakob disease (vCJD), characterised by abundant florid plaques and type 4 disease-related prion protein (PrPsc) in brain, have been homozygous for methionine at polymorphic residue 129 of PRNP. The distinctive neuropathological and molecular phenotype of vCJD can be faithfully recapitulated in Prnp null transgenic mice homozygous for human PrP M129 but not V129 where a distinct prion strain is propagated. We have modelled in transgenic mice, susceptibility of 129MV heterozygotes, the commonest PRNP genotype, comprising 51% of the UK population. We show that, remarkably, propagation of type 4 PrPsc was not associated with characteristic vCJD neuropathology. Depending upon the source of the inoculum these mice can develop four distinct disease phenotypes after challenge with BSE prions or vCJD (human passaged BSE) prions. vCJD-challenged mice had higher attack rates of prion infection than BSE-challenged recipients. These data argue that human PRNP 129 heterozygotes will be more susceptible to infection with vCJD prions than to cattle BSE prions, and may present with a neuropathological phenotype distinct from vCJD.
AD Emmanuel A. Asante, Jacqueline M. Linehan, Ian Gowland, Susan Joiner, Katie Fox, Sharon Cooper, Olufumilayo Osiguwa, Michelle Gorry, Julie Welch, Richard Houghton, Melanie Desbruslais, Sebastian Brandner, Jonathan D. F. Wadsworth, John Collinge (j.collinge@prion.ucl.ac.uk), MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
SP englisch
PO Italien