NR ATEX
AU Telling,G.C.; Browning,S.R.; Green,K.; Angers,R.C.; Mason,G.L.; Seward,T.; Green,M.; Eliason,G.A.J.; Mathiason,C.K.; Hoover,E.
TI Transgenetic studies of chronic wasting disease - an overview
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-02
PT Konferenz-Vortrag
AB Our long-term objectives are to use transgenic (Tg) approaches to study how PrP primary structure and prion strain properties influence CWD transmission barriers, to address the origins of CWD and the prevalence of CWD strains, to determine the mechanism of prion transmission among cervids and to assess the risk that CWD prions pose to humans and livestock. Tg mice expressing cervid (Cer) PrP [Tg(CerPrP)] were uniformly susceptible to CWD prions and developed neurologic dysfunction and neuropathologic features of CWD as early as ~160 days post infection. (Browning et al., 2004) Transmission studies indicated that the same prion strain caused CWD in the analyzed mule deer and elk, while studies in Tg mice expressing different CerPrP polymorphisms showed that leucine at the position 132 is highly protective to CWD prions derived from cervids homozygous for methionine (M/M) at this position. To optimize CWD susceptibility and to address the role of the hypothesized protein X, we engineered Tg mice expressing chimeric mouse/cervid PrP containing amino acids predicted to facilitate binding of PrPc with protein X, while at the same time enhancing interactions between transgene-encoded PrPc and cervid PrPsc. While such Tg(MCerB+C) mice were unexpectedly resistant to CWD and susceptible to mouse-adapted RML scrapie prions, the resulting chimeric MCerB+C prions induced by RML produced disease following transmission to Tg(CerPrP) mice; Tg(CerPrP) mice were also susceptible to prions from scrapie-affected sheep. Addressing the mechanism of CWD transmission will ultimately lead to better CWD control in cervid populations and allow more accurate assessments of the risks posed to humans and livestock from exposure to CWD prions. Our studies also further our understanding of the molecular events underlying prion propagation, species barriers and prion strains that will ultimately result in rational therapeutic and diagnostic approaches for human and animal prion diseases.
AD G.C.Telling, S.R.Browning, K.Green, R.Angers, Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA; G.L.Mason, Veterinary Diagnostic Laboratory, Colorado State University, Fort Collins, CO 80525, USA; G.C.Telling, T.Seward, Sanders Brown Center on Aging, University of Kentucky, USA; G.C.Telling, Department of Neurology, University of Kentucky, USA; G.C.Telling, Graduate Center for Gerontology, University of Kentucky, USA; M.Green, University of Kentucky Transgenic Facility, USA; G.A.J.Eliason, C.Mathiason, E.Hoover, Department of Microbiology, Immunology and Pathology, Colorado State University, USA; S.R.Browning, Present address: Department of Infectiology, Scripps Research Institute, Jupiter, Florida, USA
SP englisch
PO Deutschland