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From: TSS ()
Subject: vCJD prion acquires altered virulence through trans-species infection
Date: February 19, 2006 at 8:57 am PST

vCJD prion acquires altered virulence through trans-species infection

Masahiro Asanoa, Shirou Mohrib, James W. Ironsidec, Mamoru Itod, Norikazu Tamaokid and Tetsuyuki Kitamotoa, ,

aDivision of CJD Science and Technology, Department of Prion Research, Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai 980-8575, Japan
bLaboratory of Biomedicine, Center of Biomedical Research, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan
cNational Creutzfeldt–Jakob Disease Surveillance Unit, Division of Pathology, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK
dCentral Institute for Experimental Animals, 1430 Nogawa, Miyamae, Kawasaki 216-0001, Japan

Received 25 January 2006. Available online 7 February 2006.

Variant Creutzfeldt–Jakob disease (vCJD) appears to be caused by infection with the bovine spongiform encephalopathy (BSE) agent. To date, all patients with vCJD are homozygous for methionine at codon 129 of the PrP gene. To investigate the relationship between polymorphism at codon 129 and susceptibility to BSE or vCJD prions, we performed splenic follicular dendritic cell assay with humanized knock-in mice through peripheral infection. All humanized knock-in mice showed little or no susceptibility to BSE prions. Only the subset of humanized knock-in mice with codon 129 Met/Met genotype showed weak susceptibility by Western blotting. Surprisingly, we succeeded in the transmission of vCJD prions to humanized knock-in mice not only with codon 129 Met/Met but also with codon 129 Met/Val. Humanized knock-in mice with codon 129 Val/Val were not susceptible. The results suggest that human heterozygotes at codon 129 are also at risk for secondary infection with vCJD.

Keywords: BSE; vCJD; PrP; Polymorphism; Prion; Bovinized mouse; Humanized mouse; Follicular dendritic cell; Virulence; Traceback

Corresponding author. Fax: +81 22 717 8148.


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