NR AXHQ
AU Agrimi,U.; Nonno,R.; Di Bari,M.A.; Vaccari,G.; Fazzi,P.; Di Guardo,G.; Simson,S.; Frassanito,P.; Dell'Omo,G.; Lipp,H.P.
TI N154Y and N169S Amino Acid Substitutions in the Prion Protein Play a Major Role in Conditioning the Susceptibility of Rodent Species to Prion Diseases
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.63
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Interspecies transmission of prion diseases is limited by the "transmission barrier". Recent studies have identified the bank vole (Clethrionomys glareolus) as a rodent model very susceptible to a number of human and animal prion diseases.
Aiming at investigating in vivo the molecular basis of the high susceptibility of bank voles in interspecies transmissions and at improving the currently available mousebased models for prion diseases, we studied the transmission features of different prion sources (natural sheep scrapie, BSE and 139A) in a panel of seven rodent species showing various degrees of phylogenetic affinity and specific PrP sequence divergences.
Based in the results of transmission studies, the rodent species under investigation can be ascribed to three different groups. One group includes bank voles, field voles (Microtus agrestis) and beach mice (Peromyscus polionotus) and was characterized by: i) high susceptibility to scrapie, ii) low susceptibility to BSE, iii) extremely short incubation times with adapted strains and iv) glycoprofile's change of 139A. The second group comprises C57Bl/6 mice, wood mice (Apodemus sylvaticus), and gerbils (Meriones unguiculatus) and displayed rather opposite features: i) low or no susceptibility to scrapie, ii) relatively higher susceptibility to BSE, iii) longer incubation times with adapted strains and iv) no change in the glycoprofile of 139A. The third group includes only spiny mice (Acomys cahirinus) which showed a distinctive resistance to all prion sources.
Sequence comparison of PrP suggested that the variations correlating with the different transmission patterns observed were Y154N, S169N and D226E. In previous studies, Y154N and S169N substitutions were recognised as crucial in conditioning the conversion efficiency of the bank vole's PrP also in in vitro assays (Piening et al. J Biol Chem, 2006).
The taxonomy of rodents includes all the species under study in different subfamilies of Muridae. The consistency of transmission findings observed in species belonging to different taxonomic branches reinforces the deduction that amino acid residues 154 and 169 are major determinants of transmission barrier in rodent species. Moreover, the similar susceptibility exhibited by bank voles, field voles and beach mice indicates that the range of rodent models highly susceptible to TSE and easy to breed under laboratory conditions could be much wider than it currently is.
AD U. Agrimi, R. Nonno, M.A. Di Bari, G. Vaccari, P. Fazzi, S. Simson, P. Frassanito, Istituto Superiore di Sanità, Dep. Food Safety and Veterinary Public Health, Italy; G. Di Guardo, University of Teramo, Department of Comparative Biomedical Sciences, Italy; G. Dell'Omo, H.-P. Lipp, University of Zürich, Institute of Anatomy & Center for Neuroscience, Switzerland
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: Prion protein amino acid determinants of differential susceptibility and molecular feature of prion strains in mice and voles)