BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein.
Variant Creutzfeldt-Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrP(Sc) type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.
Asante
Emmanuel A
EA
MRC Prion Unit, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK.
Linehan
Jacqueline M
JM
Desbruslais
Melanie
M
Joiner
Susan
S
Gowland
Ian
I
Wood
Andrew L
AL
Welch
Julie
J
Hill
Andrew F
AF
Lloyd
Sarah E
SE
Wadsworth
Jonathan D F
JD
Collinge
John
J
D000818:Animals; D002417:Cattle; D003062:Codon / Q000235:genetics; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism*; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011110:Polymorphism, Genetic; D011328:Prions / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism*
D003062:Codon; D011328:Prions