Transmission of atypical scrapie to homozygous ARQ sheep

Abstract

Two Cheviot ewes homozygous for the A136L141R154Q171 (AL141RQ) prion protein (PrP) genotype were exposed intracerebrally to brain pools prepared using four field cases of atypical scrapie from the United Kingdom. Animals were clinically normal until the end of the experiment, when they were culled 7 years post-inoculation. Limited accumulation of disease-associated PrP (PrPSc) was observed in the cerebellar molecular layer by immunohistochemistry, but not by western blot or enzyme-linked immunosorbent assay. In addition, PrPSc was partially localized in astrocytes and microglia, suggesting that these cells have a role in PrPSc processing, degradation or both. Our results indicate that atypical scrapie is transmissible to AL141RQ sheep, but these animals act as clinically silent carriers with long incubation times.

Identification of the first case of atypical scrapie in Japan

“…2E) [22]. Association of PrP Sc with either astrocytes or microglia [23] was not detected in the brainstem (data not shown), agreeing with other reports of atypical scrapie cases [3, 25]. Short rod-shaped positive staining against Lm was located in the necrotic lesions (Fig.…”

“…Sodium sulfate–polyacrylamide gel electrophoresis was then performed using NuPage pre-cast 12% Bis-Tris gels in MES running buffer (Invitrogen, Carlsbad, CA, U.S.A.). The blotted membranes were probed with the monoclonal antibody (mAb) P4 (R-Biopharm, Darmstadt, Germany) according to a previously described method [23]. IHC for PrP Sc was performed using the mAb T1 [27] or F99/97.6.1 (VMRD, Pullman, WA, U.S.A.) as previously described [22,23,24].…”

“…The blotted membranes were probed with the monoclonal antibody (mAb) P4 (R-Biopharm, Darmstadt, Germany) according to a previously described method [23]. IHC for PrP Sc was performed using the mAb T1 [27] or F99/97.6.1 (VMRD, Pullman, WA, U.S.A.) as previously described [22,23,24]. Additionally, formalin-fixed and paraffin-embedded tissue sections were stained with an anti- Listeria monocytogenes (Lm) polyclonal antibody [1] and a secondary Alexa Fluor 546-conjugated antibody for dual immunofluorescence.…”

Review: Update on Classical and Atypical Scrapie in Sheep and Goats

“…137 Atypical scrapie does experimentally transmit to sheep with the AL 141 RQ haplotype but with very long incubation periods without clinical signs. 123 Furthermore, sheep with the ARR haplotype, which confers resistance to classical scrapie and is the cornerstone of genotype-based eradication programs, do not appear to be protected against developing atypical scrapie. 41,137 Figures 7-10.…”

First case of atypical scrapie in a goat in Japan

“…The animals expressing the A 136 H 154 Q 171 allele, which is strongly associated with atypical scrapie [5], constitute 0.3% of goats in Japan [14]. Since this disease has demonstrated its transmissibility to other animals [22], continuous monitoring is still required for better understanding the incidence of atypical scrapie in Japan and preventing the spread of disease in advance.…”