title: Pathogenic human prion protein rescues PrP null phenotype in transgenic mice.
abstract: Infectious prion diseases may be acquired, sporadic or inherited in their aetiology. Inherited prion diseases are caused by coding mutations in the prion protein (PrP) gene. We investigated whether one of the commonest of these mutations, E200K, results in a functionally inactive prion 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.
authors.affiliation: MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Asante
authors.forename: Yuan-Gen
authors.initials: YG
authors.lastname: Li
authors.forename: Ian
authors.initials: I
authors.lastname: Gowland
authors.forename: John G R
authors.initials: JG
authors.lastname: Jefferys
authors.forename: John
authors.initials: J
authors.lastname: Collinge
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D006624:Hippocampus / Q000473:pathology / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010641:Phenotype; D011328:Prions / Q000235:genetics* / Q000502:physiology
chemical_list: D011328:Prions