NR AWCG
AU Bishop,M.T.; Manson,J.C.
TI Investigation of human TSE strains by transmission to transgenic mice expressing human prion protein - the "Humtrans" Neuroprion Project
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-05
PT Konferenz-Poster
AB For the purpose of human TSE surveillance it is beneficial to classify cases according to the clinical and pathological characteristics. If atypical forms of sporadic CJD or variant CJD occur this characterisation is important, as such cases may change the currently held ideas on the occurrence of such diseases. Bioassay in transgenic mouse lines is often used for such case analysis and therefore our three lines expressing human prion protein (with variation at codon 129) can be used for such work. We have used gene targeting to generate MM and VV genotype inbred lines that can be crossed to produce the MV genotype. They express physiological levels of human PrPc and are more likely to develop clinical TSE after inoculation with sCJD than the wildtype line used for transgenic line production (129Ola). Inoculation of human transgenic mice with typical cases of vCJD and sCJD (all six Parchi / Gambetti types) and subsequent subpassage will produce a dataset for cross-comparison when investigating atypical cases. NeuroPrion funding for the 'HUMTRANS' project has allowed breeding stocks of these human transgenic mice to be produced in other European laboratories allowing for greater number of cases to be transmitted, together with cases specific to those countries. Preliminary strain investigation of sporadic CJD by transmission to these mice has shown that the most common type (MM genotype; PrPsc type 1) is the most efficiently transmitted. MM and MV genotype mice develop clinical TSE disease after similar incubation periods, and before the VV mice show symptoms. Further details of transmission experiments carried out by the UK IAH Neuropathogenesis Unit in Edinburgh will be presented.
AD M.T. Bishop: UK National CJD Surveillance Unit, Western General Hospital, Edinburgh, UK; J.C. Mason: Institute for Animal Health, Neuropathogenesis Unit, Kings Buildings, Edinburgh, UK. E-mail: M.Bishop@ed.ac.uk
SP englisch
PO Italien