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Revista Romana de Boli Infectioase | Volumul XVII, Nr. 2, An 2014
ISSN 1454-0398  |  e-ISSN 2069-6175
ISSN-L 1454-0398

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Spontaneous Generation of Infectious Prion Disease in Transgenic Mice

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We generated transgenic mice expressing bovine cellular prion protein (PrPc) with a leucine substitution at codon 113 (113L). This protein is homologous to human protein with mutation 102L, and its genetic link with Gerstmann–Sträussler–Scheinker syndrome has been established. This mutation in bovine PrPc causes a fully penetrant, lethal, spongiform encephalopathy. This genetic disease was transmitted by intracerebral inoculation of brain homogenate from ill mice expressing mutant bovine PrP to mice expressing wild-type bovine PrP, which indicated de novo generation of infectious poisons. Our findings demonstrate that a single amino acid change in the PrP sequence can induce spontaneous generation of an infectious prion disease that differs from all others identified in hosts expressing the same PrPc sequence. These observations support the view that a variety of infectious prion strains might spontaneously emerge in hosts displaying random genetic PrPc mutations.

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