Genetic Resistance to Scrapie Infection in Experimentally Challenged Goats

Caprine PrP variants harboring Asp-146, His-154 and Gln-211 alleles display reduced convertibility upon interaction with pathogenic murine prion protein in scrapie infected cells

“…Based on the outcomes of intracerebral inoculations, Lys-222 was associated with the highest, albeit not absolute, degree of protection. 26 The molecular basis of scrapie-protective PrP variants has not been elucidated yet. However, substantial evidence attributes reduced conversion efficiency to resistant PrP variants, as the highly protective Ala-136,Arg-154,Arg-171 variant was found to constitute only a minor fragment of the PrP SC molecules detected in the brains of scrapie-affected sheep carrying the Ala-136,Arg-154,Arg-171/Val-136,Arg-154,Gln-171 genotype.…”

“…11,[21][22][23] These alleles' relative low occurrence frequency among herds and/or goat breeds examined in field studies, suggests that additional investigations within the context of a well defined experimental scheme, including sufficient test samples and controls, are required prior to gaining further conclusive information on their effects. Different experimental approaches, utilizing either in vitro 24 or in vivo [25][26][27][28] methodologies, have been used toward this direction.…”

“…24 In parallel, in vivo studies were initialized on either transgenic mice harboring caprine Prnp alleles, 25 or on experimentally challenged goats carrying the genotypes of interest. [26][27][28] In the present work we report the in vitro study of murine-caprine PrP chimeras consisting of the mature caprine Prnp sequence and carrying the alleles of interest, in a murine cell model of scrapie. Upon interaction of exogenously expressed proteins with endogenous murine PrP SC , conformational conversion of the studied variants occurs.…”

A transfectant RK13 cell line permissive to classical caprine scrapie prion propagation

“…6 Goats homozygous for haplotypes 1 and 2 are highly susceptible to scrapie infection. 5,7 Classical caprine scrapie prion inoculation studies using kids as recipients revealed that polymorphisms of PRNP at codon 146 (serine [ 7,8 A recent goat population screening study in the UK and our experimental caprine scrapie inoculation study in goats found that a PRNP polymorphism at codon 127 [S, haplotype 3] is associated with a prolonged incubation period. 9,10 Although a polymorphism at codon 142 (methionine [M], haplotype 4) was associated with increased resistance to scrapie infections, 10 experimental caprine scrapie inoculation in goats with I/M 142 provided only a moderate increase in incubation period.…”

“…9,10 Although a polymorphism at codon 142 (methionine [M], haplotype 4) was associated with increased resistance to scrapie infections, 10 experimental caprine scrapie inoculation in goats with I/M 142 provided only a moderate increase in incubation period. 7 Traditionally, mouse bioassays have been utilized to assess prion infectivity, infectious titers and strain typing, but depending on the nature and the origin of the prions, bioassays can take months to years to produce clinical disease. As an alternative, a recent study suggests an "ovinized" model cell culture system achieved equivalent sensitivity as an "ovinized" transgenic mouse bioassay in detecting brainderived classical ovine scrapie prions but within a month post-inoculation.…”