SCRAPIE IN MICE DEFICIENT IN APOLIPOPROTEIN-E OR GLIAL FIBRILLARY ACIDIC PROTEIN

In the prion diseases, extensive reactive gliosis is often found to be out of proportion to the degree of apparent neuronal damage. To evalu ate the role of astrocytic gliosis in experimental scrapie of the mous e, we inoculated mice deficient in apolipoprotein E (apoE) or the glia l fibrillary acidic protein (GFAP) with mouse prions. The expression o f both apoE and GFAP in astrocytes increases as part of the reactive g liosis that accompanies scrapie. Null mice deficient in either apoE or GFAP inoculated with prions exhibited incubation times indistinguisha ble from untargeted control mice. The level of PrPSc and its regional deposition in the brains of ill mice deficient in either protein were also similar to control mice. Our findings demonstrate that neither ap oE nor GFAP participates in the pathogenesis of the disease or in the production of PrPSc.