Research studies showed that the polymorphisms in prion protein gene (PRNP) were associated with susceptibility to prion diseases in several animals, including humans and mouse. Several mouse strains carried natural PRNP mutations which had been identified and these could provide as animal models for human prion diseases. In this study, the genetic polymorphisms of PRNP in six common mouse strains were investigated. The experimental mice included KM mouse, ICR mouse, DBA mouse, C3H/He mouse, C57BL mouse and BALB mouse. The results showed only one new polymorphism was identified compared with the reference sequence. The identified new mutation site was C564T and it was homozygous, but this locus did not result in amino acid change. Sequence analyses suggested that these six mouse strains were susceptible to prion diseases and are suitable as susceptibility models of prion diseases.