Abstract
BackgroundThe United States control program for classical ovine scrapie is based in part on the finding that infection is typically spread through exposure to shed placentas from infected ewes. Transmission from goats to sheep is less well described. A suitable rodent model for examining the effect of caprine scrapie isolates in the ovine host will be useful in the ovine scrapie eradication effort. In this study, we describe the incubation time, brain lesion profile, glycoform pattern and PrPSc distribution patterns in a well characterized transgenic mouse line (Tg338) expressing the ovine VRQ prion allele, following inoculation with brain from scrapie infected goats.ResultsFirst passage incubation times of caprine tissue in Tg338 ovinized mice varied widely but second passage intervals were shorter and consistent. Vacuolation profiles, glycoform patterns and paraffin-embedded tissue blots from terminally ill second passage mice derived from sheep or goat inocula were similar. Proteinase K digestion products of murine tissue were slightly smaller than the original ruminant inocula, a finding consistent with passage of several ovine strains in previous reports.ConclusionsThese findings demonstrate that Tg338 mice propagate prions of caprine origin and provide a suitable baseline for examination of samples identified in the expanded US caprine scrapie surveillance program.
Highlights
The United States control program for classical ovine scrapie is based in part on the finding that infection is typically spread through exposure to shed placentas from infected ewes
The caprine PRNP gene is highly polymorphic [12,13] and there is no standard nomenclature for naming alleles
Considerable variation is noted among transgenic strains, with differences in outcome associated with route of inoculation [28,29], transgene sequence of the regulatory and coding regions of PRNP [30], and transgene expression level [31]
Summary
The United States control program for classical ovine scrapie is based in part on the finding that infection is typically spread through exposure to shed placentas from infected ewes. Scrapie has not demonstrated zoonotic potential, the introduction of vCJD through exposure to domestic animal food products has led to a call for global eradication of all animal TSEs. TSEs are characterized by accumulation of a relatively protease resistant isoform (PrPSc) of the normal cellular prion protein (PrPc), encoded by the PRNP gene [4]. The transmissible agent, referred to as a prion, is uniquely proteinaceous [5] and composed largely of PrPSc. In all TSEs, prions and PrPSc accumulate in the central nervous system but significant accumulation occurs in the lymphoid tissue and placenta [6,7] of sheep and goats with classical scrapie. Classical ovine scrapie is apparently transmitted by oral or mucosal exposure to prions shed in the placenta, blood and/or milk of infected postparturient ewes [8]. Selection for relatively resistant breeding stock has the potential of accelerating eradication of ovine scrapie from domestic flocks
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