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J Clin Pathol 2004;57:647-650 doi:10.1136/jcp.2003.012203
  • Short report

Resistance to scrapie in PrP ARR/ARQ heterozygous sheep is not caused by preferential allelic use

  1. P A Caplazi1,
  2. K I O’Rourke2,
  3. T V Baszler1
  1. 1Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA
  2. 2United States Department of Agriculture, Agricultural Research Service, Animal Disease Research Unit, Pullman, WA 99164-7030, USA
  1. Correspondence to:
 Dr T Baszler
 Department of Veterinary Microbiology and Pathology, Bustad Hall, Washington State University, Pullman, WA, 99164-7040, USA; baszlertvetmed.wsu.edu
  • Accepted 12 December 2003

Abstract

Background: In sheep, susceptibility to scrapie, which is similar to human prion diseases such as Kuru and variant Creutzfeldt-Jakob disease (vCJD), is determined by prion protein (PrP) gene (Prnp) polymorphisms. Sheep with genotype ARQ/ARQ, denoting polymorphisms at codons 136, 154, and 171, are susceptible, whereas those with genotypes ARR/ARQ and ARR/ARR are resistant, indicating dominance of ARR over the ARQ allele.

Aims: Based on familial CJD E200K, 129V, where preferential use of the 200E allele in EK heterozygous individuals confers resistance, heterozygous ARR/ARQ sheep were used to test the hypothesis that resistance is caused by preferential use of the ARR allele.

Methods: After assessment of equivalent PrP expression across genotypes, allele use was analysed by sequencing reverse transcription polymerase chain reaction derived DNA clones containing the Prnp gene coding sequence.

Results: The ARR to ARQ ratio was 1.1 in 133 clones, representing Prnp mRNA from three ARR/ARQ sheep, indicating equal use of both alleles.

Conclusions: Dominance of the resistant associated allele in sheep scrapie involves mechanisms other than the absence of PrP derived from the disease associated ARQ allele.

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