NR AWQX
AU Yokoyama,T.; Masujin,K.; Iwamaru,Y.; Imamura,M.; Yoshiba,S.; Takata,M.; Shimizu,Y.; Shinagawa,M.; Mohri,S.
TI Alteration in the biological characteristics of BSE prions was monitored by their incubation period in transgenic mice
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PR-37
PT Konferenz-Poster
AB Bovine spongiform encephalopathy (BSE) is a neurodegenerative disorder, which naturally affects cattle. However it also can be transmitted to a wide range of species including humans, where it appears as variant Creutzfeldt-Jakob disease. BSE prion has been transmitted to mice, but not to hamsters. Therefore, we analyzed the mechanisms responsible for species barrier in BSE prion by using mouse and hamster chimeric-prion protein (PrPc) expressed transgenic (Tg) mice (MH2M and MHM2). The brain homogenate of BSE cattle or BSE-passaged mice was intracerebrally inoculated into MH2M, MHM2, tga20 and TgHaNSE mice and the incubation periods of the prions in each mouse were determined. The MHM2 and tga20 mice were susceptible to the BSE prion, but not the MH2M and TgHaNSE mice. The amino acid substitutions between MH2M and MHM2 showed that the species barrier of hamsters against BSE prion was attributable to PrP131-188 (I138L, Y154N, S169N). However, after a single passage to the wild-type mouse, the BSE prion gained transmissibility to all Tg mice. Although, the shortened of the incubation period of BSE prion in the wild-type mice required at least 3 passages, the incubation period of BSE prion in the Tg mice was not altered from mouse-passage history. The prion adaptation process for overcoming the species barrier might comprise several steps--one of these is associated with PrPc while the other is not. Furthermore, the characteristics of the BSE prion that was passaged in cattle PrPc expressed Tg (TgBoPrP) mice were analyzed (BSE/TgBoPrP). The incubation period in the MHM2 with the BSE/TgBoPrP prion was approximately 220 days, which was different from the MHM2 with BSE prion (approximately 400 days). Although the mechanisms remained unclear, BSE/TgBoPrP showed distinctively different biological characteristics from the BSE of the cattle brain. Incubation time assay using a set of Tg mice could offer an effective parameter for monitoring the alteration of prion characteristics.
AD Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Japan. E-mail: tyoko@affrc.go.jp
SP englisch
PO Italien