Mice devoid of prion protein have cognitive deficits that are rescued by reconstitution of PrP in neurons.
Prion protein (PrP(C)) is a constituent of most normal mammalian cells and plays an essential role in the pathogenesis of transmissible spongiform encephalopathies (TSE). However, the normal cellular function of PrP(C) remains unclear. Here, we document that mice with a selective deletion of PrP(C) exhibited deficits in hippocampal-dependent spatial learning, but non-spatial learning remained intact. mPrP-/- mice also showed reduction in paired-pulse facilitation and long-term potentiation in the dentate gyrus in vivo. These deficits were rescued in transgenic mPrP-/- mice expressing PrP(C) in neurons under control of the neuron-specific enolase (NSE) promoter indicating that they were due to lack of PrP(C) function in neurons. The deficits were seen in mPrP-/- mice with a homogeneous 129/Ola background and in mPrP-/- mice in the mixed (129/Ola x C57BL/10) background indicating that these abnormalities were unlikely due to variability of background genes or alteration of the nearby Prnd (doppel) gene.
Criado
José R
JR
Department of Neuropharmacology (TPC-10), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. jcriado@scripps.edu
Sánchez-Alavez
Manuel
M
Conti
Bruno
B
Giacchino
Jeannie L
JL
Wills
Derek N
DN
Henriksen
Steven J
SJ
Race
Richard
R
Manson
Jean C
JC
Chesebro
Bruce
B
Oldstone
Michael B A
MB
D000682:Amyloid / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D000818:Animals; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D000682:Amyloid; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors