Objective To create transgenic mice expressing hamster- and human-PRNP as a model for understanding the physiological function and pathology of prion protein (PrP),as well as the mechanism of cross-species transmission of transmissible spongiform encephalopathies (TSEs).Methods Hamster and human-PRNP transgenic mice were established by conventional methods.The copy number of integrated PRNP in various mouse lines was mapped by real-time PCR.PRNP mRNA and protein levels were determined by semi-quantitative RT-PCR,real-time RT-PCR,and western blot analysis.Histological analyses of transgenic mice were performed by hematoxylin and eosin (H & E) staining and immunohistochemical (IHC) methods.Results Integrated PRNP copy number in various mouse lines was 53 (Tg-haPrP1),18 (Tg-huPrP1),3 (Tg-huPrP2),and 16 (Tg-huPrP5),respectively.Exogenous PrPs were expressed at both the transcriptional and translational level.Histological assays did not detect any abnormalities in brain or other organs.Conclusion We have established one hamster-PRNP transgenic mouse line and three human-PRNP transgenic mouse lines.These four transgenic mouse lines provide ideal models for additional research.