Scrapie-infected transgenic mice expressing a laminin receptor decoy mutant reveal a prolonged incubation time associated with low levels of PrPres.
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.
Pflanz
Heike
H
Laboratorium für Molekulare Biologie, Genzentrum, Institut für Biochemie der LMU München, München, Germany.
Vana
Karen
K
Mitteregger
Gerda
G
Renner-Müller
Ingrid
I
Pace
Claudia
C
Küchenhoff
Helmut
H
Kretzschmar
Hans A
HA
Wolf
Eckhard
E
Weiss
Stefan
S