Accordingly, a large number of PrP transgenic mouse lines have been produced, either by random transgenesis on a PrP−/− background or direct knockin replacement of the endogenous mouse PrP gene, with a specific prion protein transgene of interest, that harbours mutations associated with genetic forms of human prion disease, or that carry alterations in the PrP polypeptide backbone. This evidence concerns the gene PRNP and prion disease.