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Volume 19, Number 11—November 2013

Atypical Scrapie Prions from Sheep and Lack of Disease in Transgenic Mice Overexpressing Human Prion Protein

Jonathan D.F. WadsworthComments to Author , Susan Joiner, Jacqueline M. Linehan, Anne Balkema-Buschmann, John Spiropoulos, Marion M. Simmons, Peter C. Griffiths, Martin H. Groschup, James Hope, Sebastian Brandner, Emmanuel A. Asante, and John Collinge
Author affiliations: University College London, London, UK (J.D.F Wadsworth, S. Joiner, J.M. Linehan, S. Brandner, E.A. Asante, J. Collinge); Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany (A. Anne Balkema-Buschmann, M.H. Groschup); Animal Health and Veterinary Laboratories Agency, Addlestone, UK (J. Spiropoulos, M.M. Simmons, P.C. Griffiths, J. Hope)

Main Article

Table 3

Survival times of transgenic human PrP 129MM mice after inoculation of cattle BSE, vCJD, or classical CJD prions*

Transmission data
129MM Tg35 mice 129MM Tg35c mice
Inocula source code
Prion agent
Attack rate†
Survival, d‡
Attack rate†
Survival, d‡
MRC I038 Cattle BSE 8/20 263,316,333,344,389,400, 411, 468 488, 578, 593, 627–876 (9)§ 5/12 484, 611–853 (11
MRC I344 vCJD 7/7 342, 432, 487,516, 650–726 (3) 12/12 378, 447, 558, 586, 628–793 (8)#
MRC I026 Classical CJD** 7/7 215,222,222,222,222,228,228†† 9/9 223,223,223,223,226,226,226,

*PrP, prion protein; MRC, Medical Research Council; BSE, bovine spongiform encephalopathy; vCJD, variant Creutzfeldt-Jakob disease; CJD, Creutzfeldt-Jakob disease.
†All mice were inoculated with 30 μL of 1% (w/v) brain homogenate. Attack rate is defined as the total number of both clinically affected and subclinically infected mice as a proportion of the number of inoculated mice. Subclinical prion infection was assessed by immunohistochemical examination of brain for abnormal PrP deposition and analysis of 10% brain homogenate for disease-related PrP (PrPSc)by proteinase K digestion and immunoblotting.
‡The interval between inoculation and culling because of intercurrent illness, clinical prion disease, senescence, or termination of the experiment in days. Death dates of individual mice are shown together with the range for mice surviving beyond 600 d with the number of mice in this range shown in parentheses.
§Affected mice were culled at 316, 333, 344,389,400, 468, 578, and 593 d postinoculation. Mice culled at 344 and 468 d had clinical prion disease.
¶Affected mice were culled at 700, 720, 798, 817 and 853 d post-inoculation. The mouse culled at 720 d had clinical prion disease.
#Two mice with clinical prion disease were culled at 558 and 749 d.
**Iatrogenic CJD (dura mater), PRNP codon 129 methionine homozygous with type 2 PrPSc by the London classification (33).
††All mice had clinical prion disease.

Main Article

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