Mice with gene targetted prion protein alterations show that Prnp, Sinc and Prni are congruent

Richard C. Moore, James Hope, Patricia A McBride, Irene McConnell, James Selfridge, David W Melton, Jean C Manson

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)118-25
Number of pages8
JournalNature Genetics
Issue number2
Publication statusPublished - Feb 1998


  • Alleles
  • Animals
  • Brain/metabolism
  • Brain/pathology
  • Codon
  • Genetic Variation
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Point Mutation
  • Prions/biosynthesis
  • Prions/chemistry
  • Prions/genetics
  • Scrapie/genetics
  • Scrapie/pathology
  • Species Specificity


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