Pathogenic human prion protein rescues PrP null phenotype in transgenic mice

Infectious priori diseases may be acquired, sporadic or inherited in their aetiology. Inherited priori diseases are caused by coding mutations in the priori protein (PrP) gene. We investigated whether one of the commonest of these mutations, E200K, results in a functionally inactive priori protein by expressing human PrP 200K in transgenic mice homozygous for murine PrP null alleles. We examined the intrinsic properties of hippocampal CA1 pyramidal cells in these mice by measuring the resting potential, time constants and amplitude of the slow after-hyperpolarisation (AHP). These mice show rescue of the reduced slow AHP electrophysiological phenotype found in PrP null mice. Using the AHP as a marker for PrP function, we conclude that this pathogenic PrP mutation, does not significantly affect the normal neuronal function of PrP. (C) 2004 Elsevier Ireland Ltd. All rights reserved.