Publication Date:
2004-11-13
Description:
Variant Creutzfeldt-Jakob disease (vCJD) is a unique and highly distinctive clinicopathological and molecular phenotype of human prion disease associated with infection with bovine spongiform encephalopathy (BSE)-like prions. Here, we found that generation of this phenotype in transgenic mice required expression of human prion protein (PrP) with methionine 129. Expression of human PrP with valine 129 resulted in a distinct phenotype and, remarkably, persistence of a barrier to transmission of BSE-derived prions on subpassage. Polymorphic residue 129 of human PrP dictated propagation of distinct prion strains after BSE prion infection. Thus, primary and secondary human infection with BSE-derived prions may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadsworth, Jonathan D F -- Asante, Emmanuel A -- Desbruslais, Melanie -- Linehan, Jacqueline M -- Joiner, Susan -- Gowland, Ian -- Welch, Julie -- Stone, Lisa -- Lloyd, Sarah E -- Hill, Andrew F -- Brandner, Sebastian -- Collinge, John -- New York, N.Y. -- Science. 2004 Dec 3;306(5702):1793-6. Epub 2004 Nov 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15539564" target="_blank"〉PubMed〈/a〉
Keywords:
Amyloid/genetics
;
Animals
;
Brain/pathology
;
Cattle
;
Creutzfeldt-Jakob Syndrome/genetics/*metabolism/*pathology/transmission
;
Encephalopathy, Bovine Spongiform/pathology/transmission
;
Humans
;
Methionine
;
Mice
;
Mice, Transgenic
;
Phenotype
;
Polymorphism, Genetic
;
PrPC Proteins/chemistry/*genetics/metabolism
;
PrPSc Proteins/metabolism/*pathogenicity
;
Prions
;
Protein Conformation
;
Protein Precursors/genetics
;
*Valine
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
