NR AXLU
AU Espinosa,J.C.; Alamillo,E.; Herva,M.E.; Brun,A.; Torres,J.M.
TI Transgenic Mice Expressing 5 Octarepeats Bovine PrP Show a Reduced Susceptibility to BSE but the Generated 5OR-BSE Prions Retains its Transmissibility
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.105
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Some degree of polymorphism has been described in the number of octapeptide repeats (OR) found in bovine-PrP. The most common allele harbours six OR, but in a lower proportion, five and seven OR variants can be found. By other side, PrP from other species have five OR in their amino acid sequences. The number of OR has been related to incubation times after experimental inoculations and the susceptibility to BSE infection of the five OR.
Objectives: The main aims of this work were to assay the susceptibility of transgenic mice expressing bovine PrP with five octarepeat (5OR-BoPrP-Tg mice) to BSE prions and to study the biochemical and biological properties of the new generated 5OR-BSE prions.
Methods: Susceptibility of 5OR-BoPrP-Tg mouse lines in comparison to 6OR-BoPrP-
Tg mouse lines was assessed by intracerebral inoculation of the same cattle BSE inoculum. Biochemical and histopathological properties of the new generated 5ORBSE prions were studied and then re-inoculated in other transgenic mouse lines expressing PrP from different species for its biological characterization.
Results: The attack rate and incubation period found after inoculation of BSE in 5ORBoPrP-
Tg mice indicate that the infection is less efficient than in 6OR-BoPrP-Tg mice expressing similar PrPc levels. No biochemical differences were found in the 5OR-BSE PrPres from BSE-infected 5OR-BoPrP-Tg mice when compared to 6OR-BSE PrPres. The new generated 5OR-BSE prions were transmitted in all mouse models used. Transmission efficiency of 5OR-BSE prions was similar to those of 6OR-BSE prions in all mouse models tested.
Discussion: The reduced susceptibility for BSE infection found in 5OR-BoPrP-Tg mice reflects a lower efficiency of prion replication, which is probably due to a reduced ability for transformation of 5OR-PrPc into 5OR-PrPsc. This would explain the genetic basis for the low incidence of BSE in cattle expressing 5OR-BoPrP. 5OR-BSE prions preserve the same ability to cross transmission barriers than 6OR-BSE prions.
AD J.C. Espinosa, E. Alamillo, M.E. Herva, A. Brun, J.M. Torres, CISA-INIA, Spain
SP englisch
PO Schottland