Extended scrapie incubation time in goats singly heterozygous for PRNP S146 or K222

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

“…Recently published data on transgenic mice harboring the caprine Lys-222 allele after challenge with goat-scrapie and other TSE isolates, assigned strong protection to this allele. 25 Similarly, studies on experimental transmission (oral 28 or intracerebral 27 ) of natural goat scrapie isolates in heterozygous Lys-222 goats, concluded that Lys-222 significantly extends survival time after inoculation, 28 with no signs of PrP SC deposition up to 4,5 y post-inoculation. 27 Further, protective effects were assigned to the His-154, Gln-211 and Lys-222 alleles after oral or intracerebral inoculation of goats (wild type, heterozygous or homozygous for each of these alleles) with a single naturally occurring goat scrapie isolate.…”

“…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

“…7,8 Although PrP Sc levels in inocula prepared from 2 goats with PRNP haplotypes 2,3 (animal ID: g30-75) and 1,4 (animal ID: g3558) appeared to be slightly lower than the haplotypes 1,1 or 1,2 scrapie inocula, both were inoculated with scrapie-infected (animal IDs: g3558, g30-75, g3950, g4425, and g4428,) or scrapie-uninfected (animal ID: g4111) goat brain homogenates and cell lysates were prepared 5 weeks post-inoculation. One hundred ml of cpRK13 or pcRK13 cell lysate was loaded into each well (in triplicate) and relative levels of PrP Sc accumulations were evaluated using a TSE ELISA kit (IDEXX).…”

“…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.…”