ArticleProceedings of the National Academy of Sciences of the United States of America2019
Primary structural differences at residue 226 of deer and elk PrP dictate selection of distinct CWD prion strains in gene-targeted mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 88 citations in OpenAlex.
- Distinct prion conformers from brain and peripheral tissues of gene-targeted mice produce convergent CWD strain properties.PLoS pathogens · 2026Article
- Prion shedding is reduced by chronic wasting disease vaccination.PLoS pathogens · 2026Article
- Refined Transgenic Mouse Models Which Recapitulate the Natural Features of Chronic Wasting Disease With Rapid Prion Disease Onsets.The Journal of infectious diseases · 2026Article
- Prion shedding is reduced by chronic wasting disease vaccination.bioRxiv : the preprint server for biology · 2025Article
- Regulated coexpression of PrP from different species in mice impacts the replication and host range properties of prion strains.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- The Strain Properties of Korean and North American Chronic Wasting Disease Prions Are Indistinguishable.The Journal of infectious diseases · 2025Article
- Effect of primary structural variation on cervid prion protein in flexibility, stability, and spontaneous misfolding propensity.Neurobiology of disease · 2025Article
- Overview of North American Isolates of Chronic Wasting Disease Used for Strain Research.Pathogens (Basel, Switzerland) · 2025Review
- The Evolution of Experimental Rodent Models for Prion Diseases.Journal of neurochemistry · 2025Review
- Cases of Creutzfeldt-Jakob disease in young individuals: open questions regarding aetiology.Frontiers in cellular neuroscience · 2025Article
- Propagation of distinct CWD prion strains during peripheral and intracerebral challenges of gene-targeted mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Prion protein gene (PRNP) variation in German and Danish cervids.Veterinary research · 2024Article
- Transmission of Norwegian reindeer CWD to sheep by intracerebral inoculation results in an unusual phenotype and prion distribution.Veterinary research · 2024Article
- Extraneural infection route restricts prion conformational variability and attenuates the impact of quaternary structure on infectivity.PLoS pathogens · 2024Article
- Prion Seeding Activity in Plant Tissues Detected by RT-QuIC.Pathogens (Basel, Switzerland) · 2024Article
- Chronic Wasting Disease: State of the Science.Pathogens (Basel, Switzerland) · 2024Review
- Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer.PLoS pathogens · 2023Article
- Genetic modulation of CWD prion propagation in cervid PrP Drosophila.The Biochemical journal · 2023Article
- Heterozygosity for cervid S138N polymorphism results in subclinical CWD in gene-targeted mice and progressive inhibition of prion conversion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Although the unifying hallmark of prion diseases is CNS neurodegeneration caused by conformational corruption of host prion protein (PrP) to its infective counterpart, contagious transmission of chronic wasting disease (CWD) results from shedding of prions produced at high titers in the periphery of diseased cervids. While deer and elk PrP primary structures are equivalent except at residue 226, which is glutamate in elk and glutamine in deer, the effect of this difference on CWD pathogenesis is largely unknown. Using a gene-targeting approach where the mouse PrP coding sequence was replaced with elk or deer PrP, we show that the resulting GtE226 and GtQ226 mice had distinct kinetics of disease onset, prion conformations, and distributions of prions in the brains of diseased mice following intracerebral CWD challenge. These findings indicate that amino acid differences at PrP residue 226 dictate the selection and propagation of divergent strains in deer and elk with CWD. Because prion strain properties largely dictate host-range potential, our findings suggest that prion strains from elk and deer pose distinct risks to sympatric species or humans exposed to CWD. GtE226 and GtQ226 mice were also highly susceptible to CWD prions following intraperitoneal and oral exposures, a characteristic that stood in stark contrast to previously produced transgenic models. Remarkably, disease transmission was effective when infected mice were cohoused with naïve cagemates. Our findings indicate that gene-targeted mice provide unprecedented opportunities to accurately investigate CWD peripheral pathogenesis, CWD strains, and mechanisms of horizontal CWD transmission.
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