In contrast to PrPSc detection by IHC, PrPSc was not noted in immunoblotting experiments in any of the mice tested, even when the ultrasensitive PTA precipitation method was used (Fig. 1b). However, clinical signs suggestive of prion disease were observed in 7 of the 11 mice which scored positive for PrPSc by IHC (Table 4). Tremors, ataxia, wobbly gait hind leg weakness and kyphosis were among the common signs noted. Nevertheless, due to the advanced age of these mice, we could not exclude the possibility that some or all of these signs were related to old age rather than prion infection.