NR AINS
AU Moore,R.C.; Hope,J.; McBride,P.A.; McConnell,I.; Selfridge,J.; Melton,D.W.; Manson,J.C.
TI Mice with gene targetted prion protein alterations show that Prnp, Sinc and Prni are congruent
QU Nature Genetics 1998 Feb; 18(2): 118-25
KI Nat Genet. 1998 Feb;18(2):94-5. PMID: 9462729
PT journal article
AB Classical genetic analysis has identified Sinc/Prni as the major gene controlling mouse scrapie incubation time. Sinc/Prni is linked to Prnp, the gene encoding the prion protein (PrP). Prnp alleles express distinct PrP protein variants, PrP A and PrP B, which arise from codon 108L/F and 189 T/V dimorphisms. Prnp genotype segregates with incubation time length which suggests, but does not prove, that incubation time is controlled by PrP dimorphisms, and that the Sinc/Prni and Prnp loci are congruent. We have used gene targetting to construct mice in which the endogenous Prnp allele has been modified to express PrP B instead of PrP A. Challenge with a mouse-adapted BSE strain results in dramatically shortened incubation times and demonstrates that PrP dimorphisms at codon 108 and/or 189 control incubation time, and that Sinc/Prni and Prnp are congruent.
MH Alleles; Animal; Brain/metabolism/pathology; Codon; Mice; Mice, Mutant Strains; Mice, Transgenic; Molecular Sequence Data; Point Mutation; Prions/biosynthesis/chemistry/*genetics; Scrapie/genetics/pathology; Species Specificity; Support, Non-U.S. Gov't; Variation (Genetics)
AD Institute of Cell and Molecular Biology, University of Edinburgh, UK
SP englisch
PO USA