Co-presence of classical scrapie but not classical Bovine Spongiform Encephalopathy in transmissions from Dutch sheep with atypical scrapie

Two cases of atypical scrapie (AS) from Dutch sheep were passaged to WT mice and ovine and bovine prion protein (PrP) transgenic mice. Both AS isolates failed to transmit to WT mice but were successfully transmitted to ovine PrP transgenic Tg338 and Tg59 mice, carrying two different sheep PrP alleles. Western blot analysis of the brains from both mouse lines showed a similar protease-resistant band of ~6–8 kDa, which corresponded to the amino acids ~93–155 of the ovine PrP. Sagittal and coronal immunohistochemical profiles of the abnormal scrapie-associated PrP (PrPSc) in the mouse brain were constructed and revealed that PrPSc was mainly located in white matter structures in the frontal parts of the brain. Cross-passages between the Tg338 and Tg59 mice showed that the same prion strain was isolated in each mouse line. In the primary transmission of one of the AS isolates to Tg338 mice, two mice showed a very short incubation period, a mixed PrPSc profile and a classical scrapie banding pattern in the Western blot. Secondary transmission from these mice into WT VM mice and Tg338 mice revealed a similar PrPSc profile and incubation period to the classical murine scrapie strain 22A. Both primary and secondary transmissions of the two AS isolates to bovine PrP transgenic mice were negative, so we cannot confirm the previously reported co-presence of classical bovine spongiform encephalopathy (c-BSE) with AS.