title: Scrapie-infected transgenic mice expressing a laminin receptor decoy mutant reveal a prolonged incubation time associated with low levels of PrPres.
abstract: The 37-kDa/67-kDa laminin receptor (LRP/LR) was identified as a cell surface receptor for prion proteins. The laminin receptor mutant LRP102-295::FLAG interfered with PrP(Sc) propagation in murine neuronal cells presumably acting as a decoy in a transdominant negative fashion by trapping PrP molecules in the extracellular matrix. Here, we generated hemizygous transgenic mice expressing LRP102-295::FLAG in the brain. Scrapie-infected transgenic mice exhibit a significantly prolonged incubation time in comparison to scrapie-infected wild-type (FVB) mice. At the terminal stage, transgenic mice revealed significantly reduced proteinase-K-resistant PrP levels by 71% compared to wild-type mice. Our results recommend the laminin receptor decoy mutant as an alternative therapeutic tool for treatment of transmissible spongiform encephalopathies.
authors.affiliation: Laboratorium für Molekulare Biologie, Genzentrum, Institut für Biochemie der LMU München, München, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Pflanz
authors.forename: Karen
authors.initials: K
authors.lastname: Vana
authors.forename: Gerda
authors.initials: G
authors.lastname: Mitteregger
authors.forename: Ingrid
authors.initials: I
authors.lastname: Renner-Müller
authors.forename: Claudia
authors.initials: C
authors.lastname: Pace
authors.forename: Helmut
authors.initials: H
authors.lastname: Küchenhoff
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Stefan
authors.initials: S
authors.lastname: Weiss