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

Nature Genetics volume 18, pages 118–125 (1998)Cite this article

Abstract

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.

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Author notes

  1. Richard C. Moore

    Present address: University of California, Dept. of Neurology, HSE-781, 513 Parnassus Avenue, San Francisco, California, 94143-0518, USA

Authors and Affiliations

  1. Institute of Cell and Molecular Biology, University of Edinburgh, Darwin Building, King's Buildings, Mayfield Road, Edinburgh, EH9 3JR, UK

    Richard C. Moore, James Selfridge & David W. Melton

  2. Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire, RG20 7NN, UK

    James Hope

  3. Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh, EH9 3JF, UK

    Patricia A. McBride, Irene McConnell & Jean C. Manson

Authors
  1. Richard C. Moore
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Correspondence to Jean C. Manson.

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Moore, R., Hope, J., McBride, P. et al. Mice with gene targetted prion protein alterations show that Prnp, Sine and Prni are congruent. Nat Genet 18, 118–125 (1998). https://doi.org/10.1038/ng0298-118

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