The Generative Brain

Beringue V et al. 2008, Transmission of atypical bovine prions to mice transgenic for human prion protein (Emerg Infect Dis 14:1898-1901, PMID 19046515)

A short 2008 Emerging Infectious Diseases dispatch from the INRA prion group at Jouy-en-Josas, with the Turin veterinary institute, that inoculated field isolates of classical and atypical bovine prions into tg650 mice, which carry human prion protein with methionine at codon 129. L-type atypical BSE infected essentially every mouse on first passage and the disease did not change on second passage, which the authors read as no obvious transmission barrier, while classical BSE transmitted poorly at first and H-type atypical BSE did not transmit at all. The paper is one of the two 2008 studies that put the human risk question to atypical BSE in a human PrP model, the other being the Case Western study of BASE material. It is a mouse study about cattle prions and it does not show that atypical BSE has caused human disease. Information only, not medical advice.

Key facts

  • Seven authors: Vincent Beringue, Laetitia Herzog, Fabienne Reine, Annick Le Dur, Jean-Luc Vilotte and Hubert Laude at the Institut National de la Recherche Agronomique, Jouy-en-Josas, and Cristina Casalone at the Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d Aosta in Turin.
  • The dispatch appeared in Emerging Infectious Diseases volume 14, issue 12, pages 1898 to 1901, December 2008, DOI 10.3201/eid1412.080941, PMC2634647, open access, with 89 citing papers counted by Europe PMC on 21 October 2026.
  • The model was the tg650 line, which overexpresses human prion protein with methionine at codon 129 about six-fold on a mouse prion protein null background and which the authors describe as fully susceptible to the variant CJD agent; inoculation was intracerebral.
  • Four L-type isolates were tested, one Italian and three French; neurologic disease appeared in almost all mice, protease-resistant prion protein was found in all 33 brains analysed, and mean survival ran from about 574 to 703 days depending on the isolate.
  • Second passage of the Italian L-type isolate gave 11 of 11 affected mice at about 653 days, so survival did not shorten and the protein profile did not change, which is the main argument for no species barrier.
  • Three French H-type isolates were inoculated into 22 mice with no protease-resistant prion protein in any brain, and second passages in 15 further mice were also negative on blot and histoblot.
  • Classical BSE transmitted inefficiently on first passage, with protease-resistant prion protein in only 4 of 25 mice given French, German, Italian or Belgian isolates, rising to more than 80 percent on second passage at about 568 to 677 days and 8 of 8 at about 523 to 555 days on third passage, with a variant CJD like protein profile throughout.
  • The L-type protein profile differed from classical BSE and variant CJD, with a prominent monoglycosylated band, and histoblots showed finer deposits confined to particular nuclei including habenular, geniculate and dorsal thalamic nuclei and the lateral hypothalamus, while classical BSE deposits were widespread.
  • The authors concluded that the zoonotic risk from L-type BSE might be higher than from classical BSE, at least for people carrying methionine at codon 129, and called for more investigation rather than claiming a demonstrated human risk.
  • Funding came from a joint INRA and AFSSA grant, the predecessor of ANSES, and from the European Network of Excellence NeuroPrion; the French L-type and H-type isolates were supplied by A.G. Biacabe and T. Baron of the Lyon laboratory.
  • A later Emerging Infectious Diseases study from Madrid and Toulouse, published online on 21 April 2020, reproduced the two central results in different human PrP lines, a 100 percent L-type attack rate in methionine 129 mice and no H-type transmission, and added that the valine 129 variant protected strongly against L-type even in heterozygous mice.
  • A 2016 paper from the same Jouy group found no evidence that L-type BSE causes a known form of sporadic CJD in human PrP mice, which tempers the 2008 reading without contradicting the transmission result.

Timeline

  1. 2008Published in Emerging Infectious Diseases 14(12):1898-1901 as a dispatch.
  2. 2009Released in PubMed Central as PMC2634647 on 9 February 2009.
  3. 2016Jouy-en-Josas group reports no evidence that L-type BSE produces a known sporadic CJD form in human PrP mice.
  4. 2020Madrid and Toulouse groups publish a wider human PrP mouse panel online on 21 April 2020, confirming the L-type and H-type results and adding the codon 129 valine effect.
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