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Publication : Design and construction of diverse mammalian prion strains.

First Author  Colby DW Year  2009
Journal  Proc Natl Acad Sci U S A Volume  106
Issue  48 Pages  20417-22
PubMed ID  19915150 Mgi Jnum  J:155583
Mgi Id  MGI:4414744 Doi  10.1073/pnas.0910350106
Citation  Colby DW, et al. (2009) Design and construction of diverse mammalian prion strains. Proc Natl Acad Sci U S A 106(48):20417-22
abstractText  Prions are infectious proteins that encipher biological information within their conformations; variations in these conformations dictate different prion strains. Toward elucidating the molecular language of prion protein (PrP) conformations, we produced an array of recombinant PrP amyloids with varying conformational stabilities. In mice, the most stable amyloids produced the most stable prion strains that exhibited the longest incubation times, whereas more labile amyloids generated less stable strains and shorter incubation times. The direct relationship between stability and incubation time of prion strains suggests that labile prions are more fit, in that they accumulate more rapidly and thus kill the host faster. Although incubation times can be changed by altering the PrP expression level, PrP sequence, prion dose, or route of inoculation, we report here the ability to modify the incubation time predictably in mice by modulating the prion conformation.
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