RESCUE OF NEUROPHYSIOLOGICAL PHENOTYPE SEEN IN PRP NULL MICE BY TRANSGENE ENCODING HUMAN PRION PROTEIN

The prion protein (PrP) is central to the aetiology of the prion disea ses, transmissible neurodegenerative conditions of humans and animals. PrP null mice show abnormalities of synaptic neurophysiology, in part icular weakened GABA(A) receptor-mediated fast inhibition and impaired long-term potentiation in the hippocampus. Here we demonstrate that t his PrP null phenotype is rescued in mice with a high copy number of a transgene encoding human PrP but not in low copy number mice, confirm ing the specificity of the phenotype for loss of function of PrP. The ability of human PrP to compensate for loss of murine PrP will allow d irect study of the functional consequences of the 18 human PrP mutatio ns, which cause the inherited prion diseases; this phenotype can now f orm the basis of the first functional assay for PrP.