Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS

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Inherited prion disease (IPD) is caused by pathogenic mutations in the human prion protein (PrP) gene leading to the formation of lethal prions in the brain. To-date the properties of prions causing IPD and their similarities to prions causing other forms of human prion disease remain ill-defined. In the present study we have investigated the properties of prions seen in patients with Gerstmann-Sträussler-Scheinker (GSS) disease associated with the substitution of leucine for proline at amino acid position 102 (GSS P102L). We examined the ability of these prions to infect transgenic mice expressing human mutant 102L PrP, human wild-type PrP or wild-type mice. We found that GSS-102L prions have properties distinct from other types of human prions by showing that they can only infect transgenic mice expressing human PrP carrying the same mutation. Mice expressing wild-type human PrP or wild-type mouse PrP were entirely resistant to infection with GSS-102L prions. We conclude that accurate modeling of inherited prion disease requires the expression of authentic mutant human PrP in transgenic models, as other approaches may generate results that do not mirror the human disease.

Vyšlo v časopise: Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1004953
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004953

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