The Generative Brain

Wadsworth JDF et al. 2022, Humanized transgenic mice are resistant to chronic wasting disease prions from Norwegian reindeer and moose (J Infect Dis 226:933)

The main in vivo evidence that the Norwegian form of chronic wasting disease does not readily cross into human prion protein. The MRC Prion Unit at UCL, with the Norwegian Veterinary Institute and the Norwegian Institute for Nature Research, put brain material from one CWD positive reindeer and two CWD positive moose into two lines of transgenic mice carrying human prion protein, one with methionine and one with valine at codon 129, and followed them to 700 days. No mouse became ill and no mouse showed abnormal prion protein on sensitive blotting or on brain immunohistochemistry, giving an attack rate of zero in every group. The authors read this as low zoonotic potential for these isolates and note they look no more human-adapted than the North American isolates tested in the same models. Published online in the Journal of Infectious Diseases on 27 January 2021 and carried in the 1 September 2022 issue, open access under CC BY. The entry is information only and says nothing about risk to any person.

Key facts

  • Eighteen authors across three institutions: the MRC Prion Unit at UCL and the UCL Institute of Prion Diseases, the Norwegian Veterinary Institute in Oslo (Tran, Vikoren, Vage, Madslien, Benestad) and the Norwegian Institute for Nature Research in Trondheim (Ytrehus). First author Jonathan D F Wadsworth, last author John Collinge.
  • Journal of Infectious Diseases 226(5):933-937, doi 10.1093/infdis/jiab033, PMID 33502474, PMC9470110, received 1 December 2020, accepted 19 January 2021, open access under CC BY.
  • The inocula were one CWD positive reindeer brain (sample 16-04-V142), two CWD positive moose brains (16-60-P138 and 16-60-P153) and matched CWD negative brains from each species as controls.
  • Two mouse lines on a mouse prion protein knockout background were used: 129MM Tg35c, methionine at codon 129 and about twice human brain expression, and 129VV Tg152c, valine at codon 129 and about six times human brain expression. Female mice aged 6 to 8 weeks were given 30 microlitres of a 1 percent brain homogenate into the brain, in groups of about 20, and followed to a 700 day cutoff.
  • No mouse in any group developed clinical prion disease, and none showed abnormal prion protein either by high sensitivity immunoblotting after sodium phosphotungstic acid precipitation or by immunohistochemistry. The attack rate was zero of 17 to 20 in every group.
  • The reindeer brain had readily detectable PrPSc without enrichment, while the two moose brains carried roughly 10 to 50 times less and had to be concentrated from a larger volume before inoculation.
  • The authors state their own limits: a second passage from the apparently uninfected mice is needed before the barrier can be called absolute, spleen was not examined because these mice express little prion protein there, and reindeer prion protein is highly polymorphic, so further European cases with other genotypes or features should be tested.
  • The unit had already found the same human prion protein mice resistant to mule deer CWD, and other humanized lines showed no transmission from elk, mule deer or white-tailed deer isolates. The authors note that some North American isolates can seed human prion protein in vitro but argue that humanized mice and macaques are the more relevant models.
  • Funding came from the Norwegian Ministry of Agriculture through the Norwegian CWD surveillance programme, the Norwegian Veterinary Institute (project 12081-CWD) and the UK Medical Research Council (MC_U123160655 and MC_UU_00024/5 among the listed grants). A declared interest: the ICSM 35 antibody came from D-Gen Ltd, in which Collinge and Wadsworth hold roles or shares.
  • A companion in vitro study published weeks later in the same journal points the same way on human prion protein. Pritzkow and colleagues found that no cervid isolate converted human prion protein in a first round of protein misfolding cyclic amplification, and that in a second round the three North American isolates did while the Norwegian reindeer, red deer and moose isolates gave a zoonotic score of zero against 6 for white-tailed deer, 5 for mule deer and 4 for elk.
  • The same in vitro study pulls in the opposite direction on animal to animal spread: the Norwegian isolates were the most efficient at converting non-human prion protein, with a spillover index of 12 for reindeer and 9 for moose, and the authors read Norwegian and North American CWD as different strains with different spillover and zoonotic potential.
  • The exposure side of the question stayed open. A 2025 Emerging Infectious Diseases study from the Norwegian Veterinary Institute with Italian partners amplified prions by PMCA from every muscle type tested in 2 reindeer, 4 moose and 1 red deer with CWD, with head muscles always positive, and one moose ocular muscle transmitted disease to bank voles. The authors call for caution about human exposure through edible tissues while citing this paper as evidence against transmission to human prion protein mice.
  • Uptake as counted on 17 October 2026: Europe PMC lists 37 citing records and OpenAlex 45 citations with a field weighted citation impact of 2.41.

Timeline

  1. 2020Manuscript received by the Journal of Infectious Diseases.
  2. 2021Manuscript accepted after editorial decision on 14 January 2021.
  3. 2021Published online, open access under CC BY.
  4. 2022Pritzkow and colleagues publish the PMCA comparison of North American and Norwegian CWD in the same journal, scoring the Norwegian isolates at zero for human prion protein conversion.
  5. 2022Paper carried in the print issue, J Infect Dis 226(5):933-937.
  6. 2025Emerging Infectious Diseases publishes the Norwegian cervid muscle prion study, which cites this paper while raising the exposure question.
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