ArticleProceedings of the National Academy of Sciences of the United States of America2013
Profoundly different prion diseases in knock-in mice carrying single PrP codon substitutions associated with human diseases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The Role and Clinical Observation of Traditional Chinese Medicine in Relieving Senile Insomnia: A Systematic Review and Meta-Analysis.BioMed research international · 2022Pooled it
- PrP turnover in vivo and the time to effect of prion disease therapeutics.PLoS pathogens · 2026Article
- Characterization of prion strains and peripheral prion infectivity patterns in E200K genetic CJD patients.Acta neuropathologica · 2025Article
- The Evolution of Experimental Rodent Models for Prion Diseases.Journal of neurochemistry · 2025Review
- Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease.Stem cell reports · 2024Article
- Convergent generation of atypical prions in knockin mouse models of genetic prion disease.The Journal of clinical investigation · 2024Article
- Anti-prion drugs do not improve survival in novel knock-in models of inherited prion disease.PLoS pathogens · 2024Article
- Selective Vulnerability to Neurodegenerative Disease: Insights from Cell Type-Specific Translatome Studies.Biology · 2024Review
- Etiology matters: genetic and acquired prion diseases engage different mechanisms at a presymptomatic stage.Neural regeneration research · 2023Article
- Hypothesis: functional age and onset of autosomal dominant genetic prion disease.Theory in biosciences = Theorie in den Biowissenschaften · 2023Article
- Therapeutic Trial of anle138b in Mouse Models of Genetic Prion Disease.Journal of virology · 2023Article
- Translatome profiling in fatal familial insomnia implicates TOR signaling in somatostatin neurons.Life science alliance · 2022Article
- Distinct translatome changes in specific neural populations precede electroencephalographic changes in prion-infected mice.PLoS pathogens · 2022Article
- Virus Infection, Genetic Mutations, and Prion Infection in Prion Protein Conversion.International journal of molecular sciences · 2021Review
- Slc1a3-2A-CreERT2 mice reveal unique features of Bergmann glia and augment a growing collection of Cre drivers and effectors in the 129S4 genetic background.Scientific reports · 2021Article
- A seven-residue deletion in PrP leads to generation of a spontaneous prion formed from C-terminal C1 fragment of PrP.The Journal of biological chemistry · 2020Article
- Spontaneous generation of prions and transmissible PrP amyloid in a humanised transgenic mouse model of A117V GSS.PLoS biology · 2020Article
- Transcriptional signature of prion-induced neurotoxicity in a Drosophila model of transmissible mammalian prion disease.The Biochemical journal · 2020Article
- Experimental Models of Inherited PrP Prion Diseases.Cold Spring Harbor perspectives in medicine · 2017Review
- Genetic human prion disease modelled in PrP transgenicThe Biochemical journal · 2017Article
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7 authors at 4 institutions in 1 country.
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Abstract
In man, mutations in different regions of the prion protein (PrP) are associated with infectious neurodegenerative diseases that have remarkably different clinical signs and neuropathological lesions. To explore the roots of this phenomenon, we created a knock-in mouse model carrying the mutation associated with one of these diseases [Creutzfeldt-Jakob disease (CJD)] that was exactly analogous to a previous knock-in model of a different prion disease [fatal familial insomnia (FFI)]. Together with the WT parent, this created an allelic series of three lines, each expressing the same protein with a single amino acid difference, and with all native regulatory elements intact. The previously described FFI mice develop neuronal loss and intense reactive gliosis in the thalamus, as seen in humans with FFI. In contrast, CJD mice had the hallmark features of CJD, spongiosis and proteinase K-resistant PrP aggregates, initially developing in the hippocampus and cerebellum but absent from the thalamus. A molecular transmission barrier protected the mice from any infectious prion agents that might have been present in our mouse facility and allowed us to conclude that the diseases occurred spontaneously. Importantly, both models created agents that caused a transmissible neurodegenerative disease in WT mice. We conclude that single codon differences in a single gene in an otherwise normal genome can cause remarkably different neurodegenerative diseases and are sufficient to create distinct protein-based infectious elements.
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