NR AWEG
AU Dossena,S.; Garofoli,A.; Senatore,A.; Mangieri,M.; Tagliavini,F.; Forloni,G.; Chiesa,R.
TI Molecular characterization of the polymorphic variants of the PrP D178N mutation expressed in transgenic mice
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PR-10
PT Konferenz-Poster
AB Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD178) are clinically and neuropathologically distinct diseases linked to the D178N mutation in the gene encoding the prion protein (PrP). The disease phenotype is determined by the M/V polymorphism at codon 129 of the mutant allele: D178N/M129 segregates with FFI, while D178N/V129 is associated with CJD178. It is hypothesized that conformational differences between the polymorphic variants of D178N PrP account for this phenotypic heterogeneity. We have generated transgenic (Tg) mice that express the mouse PrP homologues of the D178N mutants (D177N/M128 and D177N/V128). Analysis of the biochemical properties of PrP extracted from the brains of Tg mice indicates that both mutants are aggregated and partially resistant to low concentrations of proteinase-K, yielding protease-resistant fragments of similar molecular size. However, D177N/V128 PrP displays higher resistance to ureainduced dissociation than D177N/M128, suggesting that the two proteins possess different oligomeric states. To investigate possible differences in the secondary/tertiary structure, we are currently applying a conformation-dependent immunoassay, which compares the accessibility of antibody epitopes in the folded and unfolded forms of PrP.
AD S. Dossena, A. Garofoli, A. Senatore, R. Chiesa: Dulbecco Telethon Institute and Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; M. Mangieri, F. Tagliavini: Istituto Neurologico Nazionale Carlo Besta, Milan, Italy; G. Forloni: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. E-mail: dossena@marionegri.it
SP englisch
PO Italien