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Unaltered susceptibility to BSE in transgenic mice expressing human prion protein
J Collinge1, M S Palmer, K C Sidle
1Department of Biochemistry and Molecular Genetics, Imperial College School of Medicine at St Mary's, London, UK.
Abstract:
Prion diseases are transmissible neurodegenerative conditions of humans and animals. Prions consist principally of a post-translationally modified form of prion protein (PrP), PrP(Sc), which is partly protease resistant. Transmission of prion diseases between species is limited by a 'species barrier' determined in part by the degree of sequence homology between host PrP and inoculated PrP(Sc) (ref.3) and by prion strain type. The epidemic of bovine spongiform encephalopathy (BSE) in the United Kingdom and other countries has led to concerns that transmission to humans may occur by dietary exposure. BSE appears to be caused by a single strain, distinct from those of natural or experimental scrapie, which is also seen in the new prion diseases of cats and ruminants that have presumably arisen from dietary BSE exposure. Here we show that transgenic mice expressing human PrP in addition to mouse PrP can generate human PrP(Sc) and 'human' prions. These mice therefore provide a model to study experimentally the species barrier limiting BSE transmission to humans. Incubation periods to BSE in transgenic mice are not shortened by expression of human PrP, and only mouse PrP(Sc) is produced in response to such challenge.
Insights
Transmissible neurodegenerative diseases, known as prion diseases, can cross species barriers. Transgenic mice expressing human prion protein (PrP) did not shorten incubation periods for bovine spongiform encephalopathy (BSE) or produce human PrP(Sc).
Area of Science:
- Neurodegenerative diseases
- Prion biology
- Transmissible spongiform encephalopathies
Background:
- Prion diseases are fatal neurodegenerative conditions affecting humans and animals.
- Prions are misfolded proteins (PrPSc) resistant to degradation.
- A species barrier typically limits prion disease transmission between different species.
Purpose of the Study:
- To investigate the potential for bovine spongiform encephalopathy (BSE) transmission to humans.
- To develop a transgenic mouse model for studying the human prion disease species barrier.
Main Methods:
- Transgenic mice expressing human prion protein (PrP) were challenged with BSE prions.
- Incubation periods and prion protein (PrP) formation in challenged mice were analyzed.
Main Results:
- Transgenic mice expressing human PrP did not exhibit shortened incubation periods when challenged with BSE.
- Only mouse PrPSc was detected in the transgenic mice, not human PrPSc, following BSE challenge.
Conclusions:
- The study suggests that human PrP expression in mice does not facilitate BSE prion replication or transmission.
- These findings contribute to understanding the species barrier for BSE transmission to humans.