Interestingly, Tg(PG14) mice expressing nine-octapeptide insertion in PrP, thus resembling the human familial prion disease, spontaneously developed a fatal neurodegenerative disorder, but they were characterized by the accumulation in the brain of weakly protease-resistant form of PrP mutant which was not infectious in animal transmission experiments [133]. This evidence concerns the gene PRNP and prion disease.