GENE-EXPRESSION IN SCRAPIE - CLONING A NEW SCRAPIE-RESPONSIVE GENE AND THE IDENTIFICATION OF INCREASED LEVELS OF 7 OTHER MESSENGER-RNA TRANSCRIPTS

To define genes associated with or responsible for the neurodegenerati ve changes observed in transmissible spongiform encephalopathies, we a nalyzed gene expression in scrapie-infected mouse brain using ''mRNA d ifferential display.'' The RNA transcripts of eight genes were increas ed 3-8-fold in the brains of scrapie-infected animals, Five of these g enes have not previously been reported to exhibit increased expression in this disease: cathepsin S, the C1q B-chain of complement, apolipop rotein D, and two previously unidentified genes denominated scrapie-re sponsive gene (ScRG)-1 and ScRG-2, which are preferentially expressed in brain tissue, Increased expression of the three remaining genes, be ta 2 microglobulin, F4/80, and metallothionein II, has previously been reported to occur in experimental scrapie, Kinetic analysis revealed a concomitant increase in the levels of ScRG-1, cathepsin S, the C1q B -chain of complement, and beta 2 microglobulin mRNA as well as glial f ibrillary acidic protein and F4/80 transcripts, markers of astrocytosi s and microglial activation, respectively, In contrast, the level of S cRG-2, apolipoprotein D, and metallothionein II mRNA was only increase d at the terminal stage of the disease. ScRG-1 mRNA was found to be pr eferentially expressed in glial cells and to code for a short protein of 47 amino acids with a strong hydrophobic N-terminal region.