NR AOQB
AU Barron,R.M.; Thomson,V.; King,D.; Melton,D.W.; Ironside,J.; Will,R.; Manson,J.C.
TI Transmission of Human TSEs to P101L Transgenic Mice
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-05
PT Konferenz-Poster
AB The transmission of human TSE disease to wild type mice is often difficult to achieve. With the exception of vCJD which transmits efficiently to wild type mice, incubation times of over 500 days and low levels of susceptibility are usually observed, and many isolates appear to be non-transmissible to mice. The expression of chimeric human/mouse PrP transgenes has facilitated the transmission of several human agents to mice, but we present here evidence that some strains of human TSE disease can be transmitted to mice which contain a proline to leucine mutation at amino acid 101 in murine PrP (101LL). Transmission of disease in the absence of any human specific sequences in the 101LL mice therefore suggests that sequence identity is not the main criteria for TSE transmissibility. Transmissions of sporadic CJD (sCJD) do not produce clinical disease in wild type mice, but TSE pathology can be detected in the brains of mice which survive over 600 days post inoculation. In contrast, clinical disease was observed in 101LL mice between 400-600 days post inoculation, and could be passaged in 101LL mice in around 170 days, but not in wild type mice. Similar results have been obtained with P102L GSS, however vCJD produced extended incubation times in 101LL mice compared to wild type mice. P105L GSS did not transmit to either line of mice, indicating that not all human TSEs are transmissible to 101LL mice. The transmissibility of human TSE disease to 101LL mice is therefore strain dependant, and does not rely on PrP sequence identity either overall, or at amino acid 101/102. The interaction of each individual TSE strain with the N-terminus of host PrP must be a critical step in the transmission of disease between species.
AD R.M. Barron, V. Thomson, D. King, J.C. Manson, Institute for Animal Health, UK; D.W. Melton, CRC Molecular Medicine Centre, UK; J. Ironside, R. Will, CJD Surveillance Unit, UK
SP englisch
PO Deutschland