For example, Tg650 mice (HuM129, sixfold PrP expression) [16] inoculated with vCJD prions develop neurological disease with a 100% attack rate, but Tg35 mice (HuM129, two-fold PrP expression) [6] and knock-in mice (replacing murine with single copy human PrP) [18] only infrequently show neurological symptoms, whilst histological and biochemical examination clearly suggests subclinical disease. This evidence concerns the gene PRNP and nervous system disorder.