PRNP and prion disease: In the case of human transgenic mice, insertion of PRNP. A series of transmission experiments by the groups of Jean Manson and Tetsuyuki Kitamoto have used gene targeting in the development of several “humanised” transgenic mice, in which the Prn-p gene was directly replaced by PRNP. These mouse lines have been used to investigate specific familial mutations associated with disease as well as extensive studies on the effect of the naturally occurring methionine (M) to valine (M) polymorphism at codon 129 on PRNP, which is a recognised risk factor for human prion diseases.