Premium
Post‐natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration
Author(s) -
Mallucci G.R.,
Ratté S.,
Asante E.A.,
Linehan J.,
Gowland I.,
Jefferys J.G.R.,
Collinge J.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.3.202
Subject(s) - neurodegeneration , biology , knockout mouse , genetically modified mouse , transgene , hippocampal formation , neuroscience , microbiology and biotechnology , loss function , phenotype , disease , gene , medicine , genetics
Prion protein (PrP) plays a crucial role in prion disease, but its physiological function remains unclear Mice with gene deletions restricted to the coding region of PrP have only minor phenotypic deficits, but are resistant to prion disease We generated double transgenic mice using the Cre– lox P system to examine the effects of PrP depletion on neuronal survival and function in adult brain Cre‐mediated ablation of PrP in neurons occurred after 9 weeks We found that the mice remained healthy without evidence of neurodegeneration or other histopathological changes for up to 15 months post‐knockout However, on neurophysiological evaluation, they showed significant reduction of afterhyperpolarization potentials (AHPs) in hippocampal CA1 cells, suggesting a direct role for PrP in the modulation of neuronal excitability These data provide new insights into PrP function Furthermore, they show that acute depletion of PrP does not affect neuronal survival in this model, ruling out loss of PrP function as a pathogenic mechanism in prion disease and validating therapeutic approaches targeting PrP.