NR AOVI
AU Laffont,I.; Hässig,R.; Haik,S.; Sazdovitch,V.; Hauw,J.J.; Faucheux,B.A.; Moya,K.L.
TI Species differences in full length and truncated PrPc in brain
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-43
PT Konferenz-Poster
AB
The majority of human brain PrPc is truncated at a.a. 111/112 and thus antibodies such as 3F4 whose epitope is a.a. 109-112 do not detect the major forms of the protein (Pan et al., J Neurochem 81: 1092, 2002). In previous studies we used mab 3F4 to analyze PrPc in hamster brain. To determine if the major form of hamster brain PrPc is truncated we used antibodies against epitopes N-terminal to (SAF 32) and C-terminal to (SAF 60) the cleavage site and compared different species by western blot.
In hamster, rat and mouse, SAF 32 and SAF 60 gave an intense signal for 36kD diglycosylated PrPc and a weaker signal for 33kD monoglycosylated PrPc. A faint band at 24kD was visible on long exposures of the films in these species. In extracts from normal human brain Val/Val at codon 129, the strongest PrPc signal was detected at 25kD with SAF 60 with a much weaker signal at for 36kD diglycosylated PrPc recognized by SAF 32. A similar pattern was observed in baboon. When we compared this pattern with material from a human brain Met/Met at codon 129 the intensity of full length 36kD was similar to the truncated ~25kD form. In marmoset (a new world primate) the pattern was similar to that observed in rodents with the full-length form the most abundant and the truncated form barely detectable. Analysis of other species showed that the most abundant form in cow and pig was the 36kD form while in sheep a stronger signal was seen at 25kD.
These results show that the major form of PrPc in rodent brain is full-length. In two old world primates a truncated form is more abundant while in a new world primate the major form is full length suggesting evolutionary differences in PrPc cleavage. The difference in the two human cases is interesting and needs further confirmation. Finally, these species differences suggest there may be limitations in extrapolating results from rodents to other species at least with regards to a role for truncated PrPc in TSE pathogenesis. Support: GIS prions.
AD Isabelle Laffont, Raymonde Hässig, Kenneth L. Moya, CEA-CNRS URA 2210, France; Stéphane Haïk, Véronique Sazdovitch, Jean-Jacques Hauw, Baptiste A. Faucheux, Laboratoire de Neuropathologie R. Escourolle, Hôpital de la Salpêtrière, France
SP englisch
PO Deutschland