Mice devoid of prion protein have cognitive deficits that are rescued by reconstitution of PrP in neurons

Abstract

Prion protein (PrPC) 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 PrPC remains unclear. Here, we document that mice with a selective deletion of PrPC 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 PrPC in neurons under control of the neuron-specific enolase (NSE) promoter indicating that they were due to lack of PrPC 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 × C57BL/10) background indicating that these abnormalities were unlikely due to variability of background genes or alteration of the nearby Prnd (doppel) gene.

Keywords

• Prion protein
• Mice
• Knockout
• Transgenic
• Hippocampus
• Spatial learning