1887

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Volume 86, Issue 10

Prion clearance in bigenic mice Free

Abstract

The clearance of prions from the brain was investigated in bigenic mice designated Tg(tTA : PrP)3, in which expression of the cellular prion protein (PrP) was regulated by oral doxycycline administration. With suppression of PrP expression, the incubation time for RML prions was prolonged almost threefold from ∼150 to ∼430 days. To determine the clearance rate of disease-causing PrP, bigenic mice were given oral doxycycline beginning 98 days after inoculation with RML prions and sacrificed at various time points over the subsequent 56 days. The half-life ( ) for PrP was ∼1·5 days in mouse brain, in reasonable agreement with the apparent of 30 h that was determined in a separate study for scrapie-infected mouse neuroblastoma (ScN2a) cells in culture. Both protease-sensitive and -resistant conformers of PrP were cleared at the same rate. The value for PrP clearance from brain was ∼18 h, which was considerably longer than the of 5 h found in ScN2a cells. The capability of the brain to clear prions raises the possibility that PrP is normally made at low levels and continually cleared, and that PrP may have a function in cellular metabolism. Moreover, these bigenic mice make it possible to determine both components of PrP accumulation, i.e. the rates of formation and clearance, for various strains of prions exhibiting different incubation times.

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2005-10-01
2024-04-19
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Prion clearance in bigenic mice
J. Gen. Virol. 86, 2913 (2005); https://doi.org/10.1099/vir.0.80947-0
/content/journal/jgv/10.1099/vir.0.80947-0
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