NR AXSE
AU Marcos-Carcavilla,A.; Calvo,J.H.; Gonzalez,C.; Moazami-Goudarzi,K.; Laurent,P.; Bertaud,M.; Hayes,H.; Beattie,A.E.; Alves,S.; Serrano,M.
TI Ovine Laminin Receptor Gene is not Part of the Scrapie Polygenic Variance but, What about its Role in the Prion Species Barrier?
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.56
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: The existence of genes other than the PRNP, has been proposed to explain both the difference in incubation periods to scrapie between sheep and mice, and the species barrier. In this regard, it has been demonstrated that the laminin receptor (LRP/LR) with the aid of heparan sulfate proteoglicans as cofactors/coreceptors is involved not only in PrPc metabolism but also in prion propagation.
Aims: Isolation and characterisation of the ovine LAMR1 gene. Determination of its exact position on the ovine genome. Evaluation of the LRP/LR relevance in the polygenetic variance described above and in the species barrier to SC and other transmissible spongiform encephalopathies (TSEs).
Methods: A BAC containing the ovine LAMR1 gene was purified and used both to determine the gene sequence, by amplifying and sequencing overlapping segments of the insert, and to localize it by FISH. The chromosomal localization was confirmed by linkage analysis. The polymorphism of the ovine LRP/LR at previously described binding domains to PrP was studied in 80 sheep of the Rasa Aragonesa breed. Although all these sheep have the same PRNP genotype (ARQ/ARQ), they showed different response to SC infection. Finally, the LRP/LR protein from man, cattle, pig, dog, cat and several rodents, deposited at GenBank, was compared with that inferred from our ovine and rabbit sequences, in order to analyse its variation among different species.
Results: The ovine LAMR1 gene has been isolated and characterized. It is localized on the ovine chromosome OAR 19q13, between CSSM06 and 2HF3B markers. All the mutations identified within the group of sheep analysed were silent. Conversely, amino acid positions 241, 272 and 290 were highly polymorphic when analysed at the interspecies level.
Conclusion. Ovine LAMR1 gene organization and localization agree with the data available in other species. Although the absence of variation at the amino acid level within the sheep group analysed rules out this receptor as responsible for the susceptibility difference between sheep with the same PRNP genotype, its possible involvement in the species barrier to SC and other TSEs should not be discarded.
AD A. Marcos-Carcavilla, INIA, Mejora Genetica Animal, Spain; J.H. Calvo, CITA, Spain; C. González, S. Alves, M. Serrano, INIA, Spain; K. Moazami-Goudarzi, P. Laurent, M. Bertaud, H. Hayes, INRA, France; A.E. Beattie, Invermay Agricultural Centre, New Zealand
SP englisch
PO Schottland