Experimental transmission of two young and one suspended bovine spongiform encephalopathy (BSE) cases to bovinized transgenic mice.

Bovine spongiform encephalopathy (BSE) is caused by a prion that primarily consists of an abnormal isoform of the prion protein (PrP Sc ). Since PrP Sc is partially resistant to proteolytic digestion, the routine diagnosis of BSE is based on the immunological detection of the proteinase K (PK)-resistant moiety of PrP Sc (PrP core ). However, transmission studies are indispensable in order to demonstrate prion infectivity and to analyze prion characteristics. Transmission experiments were accordingly performed on 2 young BSE cases (BSE/JP8, BSE/ JP9) and 1 suspected BSE case (Suspended-1) that were detected by the BSE screening program in Japan. In this study, we attempted to transmit the prion from these 3 animals by using transgenic mice overexpressing bovine PrP (TgBoPrP). In spite of the use of BSE-sensitive transgenic mice, none of the mice developed neurological signs nor accumulated PrP Sc in their brains for more than 600 days post-inoculation, even with subsequent blind passages. The results of a dilution experiment using the classical BSE prion indicated that prion infectivity in these 3 cattle was below the detection limit of 10 3.0 LD 50 /g.