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

¹ Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA
² United States Department of Agriculture, Agricultural Research Service, Animal Disease Research Unit, Pullman, WA 99164-7030, USA

Correspondence to:
Dr T Baszler
Department of Veterinary Microbiology and Pathology, Bustad Hall, Washington State University, Pullman, WA, 99164-7040, USA; baszlert{at}vetmed.wsu.edu
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.

Keywords: genetic resistance; prions; scrapie; transmissible spongiform encephalopathy

Abbreviations: CJD, Creutzfeldt-Jakob disease; Fab, antibody Fab fragment(s); FDC, follicular dendritic reticulum cell; IFA, indirect immunofluorescence assay; PCR, polymerase chain reaction; PrP, prion protein; Prnp, prion protein gene; RT, reverse transcription; TSE, transmissible spongiform encephalopathy; vCJD, Creutzfeldt-Jakob disease, new variant; WB, western blotting

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				A. Rigter and A. Bossers Sheep scrapie susceptibility-linked polymorphisms do not modulate the initial binding of cellular to disease-associated prion protein prior to conversion J. Gen. Virol., September 1, 2005; 86(9): 2627 - 2634. [Abstract] [Full Text] [PDF]