NR ATRL
AU Piening,N.; Bertsch,U.; Agrimi,U.; Kretzschmar,H.A.
TI Differences at codon 155 and 170 are responsible for the species barrier between mice and bank voles, a wild rodent species highly susceptible to scrapie
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Structure of PrP and molecular determinants of infectivity STRCT-27
PT Konferenz-Poster
AB Inoculation studies with bank voles (Clethrionomys glareolus), a wild rodent species, have revealed that compared to mice these rodents are highly susceptible to natural scrapie but show apparent resistance to BSE infection. Amino acid sequence comparison of the prion proteins of voles, mouse, sheep and cattle has identified the four amino acid residues M109, N155, N170 and E227 that are likely to be responsible for the observed species barriers. By using in vitro conversion reactions we have identified the differences at codon 155 and 170 to be mainly responsible for the species barrier between mice and voles. Amino acid composition at residue 227 was not important for the investigated species barriers. Moreover, in vitro conversion reactions revealed that mouse PrPc was converted more efficiently to its protease resistant isoform no matter if it was incubated with BSE or sheep scrapie. This difference to the in vivo data indicates that the primary amino acid sequence is not responsible for the differential susceptibility of the bank voles towards BSE and scrapie infection. Additional host factors must be responsible for differences between the data obtained in vivo and in vitro.
IN Die Rötelmaus (Rötel- oder Waldwühlmaus Clethrionomys glareolus) ist verglichen mit der normalen Hausmaus deutlich resistenter gegen BSE, aber empfänglicher für Scrapie-Infektionen. Im Gegensatz zu diesem in vivo - Befund lässt sich aber das Maus-PrPc in vitro durch BSE- und Scrapie-Prionen leichter als das PrPc der Rötelmaus umwandeln. Dies spricht für den in vivo wirksamen Einfluß mindestens eines zusätzlichen Moleküls.
AD N.Piening, U.Bertsch, H.A.Kretzschmar, Center for Neuropathology and Prion research, Ludwig-Maximilians-University, Munich, Germany; U.Agrimi, Instituto Superiore di Sanità, Rome, Italy
SP englisch
PO Deutschland