Dominant-negative inhibition of prion replication in transgenic mice.

ABSTRACT: Our discovery of dominant-negative inhibition of prion formation in cultured cells provided an explanation for the resistance of some sheep to scrapie and humans to Creutzfeldt-Jakob disease. To determine whether dominant-negative inhibition occurs in vivo, we produced transgenic (Tg) mice expressing prion protein (PrP) with either the Q167R or Q218K mutation alone or in combination with wild-type (wt) PrP. Tg(MoPrP,Q167R)Prnp(0/0) mice expressing mutant PrP at levels equal to non-Tg mice remained healthy for >550 days, indicating that inoculation with prions did not cause disease. Immunoblots of brain homogenates and histologic analysis did not reveal abnormalities. Tg(MoPrP,Q167R)Prnp(+/+) mice expressing both mutant and wt PrP did not exhibit neurologic dysfunction, but their brains rev

SUBMITTER: Perrier V 

PROVIDER: S-EPMC130589 | biostudies-literature | 2002 Oct

REPOSITORIES: biostudies-literature