MOUSE CORTICAL-CELLS LACKING CELLULAR PRP SURVIVE IN CULTURE WITH A NEUROTOXIC PRP FRAGMENT

To elucidate whether the neurotoxic effect of a prion protein fragment (PrP106-126) is in some way mediated by the cellular isoform of the p rion protein (PrPc), dissociated cortical cell cultures were prepared from mice in which the PrP gene had been disrupted (PrP0/0 mice). Cell survival after 10 days in culture was tested with an MTT assay. PrP10 6-126 applied every second day for 10 days in cultures from normal mic e resulted in the death of 34% more cells than in untreated cells. Whe n PrP106-126 was applied to cultures from mice lacking PrPc expression , survival was equal to or greater than that of untreated control cell s. These results support the notion that expression of PrPc is require d for the neurotoxic effect of PrP106-126.