Here we report that transgenic (Tg) mice carrying the PrP mutation associated with one of these diseases (fatal familial insomnia, FFI) develop severe sleep disorders and other key phenotypic features of the human disease, different from those seen in analogously generated Tg mice expressing another prion disease-associated mutation (Creutzfeldt-Jakob disease, CJD). Here, PRNP is linked to prion disease.