Abstract:
:Most transmissible spongiform encephalopathies arise either spontaneously or by infection. Mutations of PRNP, which encodes the prion protein, PrP, segregate with phenotypically similar diseases. Here we report that moderate overexpression in transgenic mice of mPrP(170N,174T), a mouse PrP with two point mutations that subtly affect the structure of its globular domain, causes a fully penetrant lethal spongiform encephalopathy with cerebral PrP plaques. This genetic disease was reproduced with 100% attack rate by intracerebral inoculation of brain homogenate to tga20 mice overexpressing WT PrP, and from the latter to WT mice, but not to PrP-deficient mice. Upon successive transmissions, the incubation periods decreased and PrP became more protease-resistant, indicating the presence of a strain barrier that was gradually overcome by repeated passaging. This shows that expression of a subtly altered prion protein, with known 3D structure, efficiently generates a prion disease.
journal_name
Proc Natl Acad Sci U S Aauthors
Sigurdson CJ,Nilsson KP,Hornemann S,Heikenwalder M,Manco G,Schwarz P,Ott D,Rülicke T,Liberski PP,Julius C,Falsig J,Stitz L,Wüthrich K,Aguzzi Adoi
10.1073/pnas.0810680105subject
Has Abstractpub_date
2009-01-06 00:00:00pages
304-9issue
1eissn
0027-8424issn
1091-6490pii
0810680105journal_volume
106pub_type
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