Enhanced levels of scrapie responsive gene mRNA in BSE-infected mouse brain

The expression of the mRNA of nine scrapie responsive genes was analyzed in the brains of FVB/N mice infected with bovine spongiform encephalopathy (B SE). The RNA transcripts of eight genes were overexpressed to a comparable extent in both BSE-infected and scrapie-infected mice, indicating a common series of pathogenic events in the two transmissible spongiform encephalopa thies (TSEs). In contrast, the serine proteinase inhibitor spi 2, an analog ue of the human alpha-1 antichymotrypsin gene, was overexpressed to a great er extent in the brains of scrapie-infected animals than in animals infecte d with BSE, reflecting either an agent specific or a mouse strain specific response. The levels of spi 2 mRNA were increased during the course of scra pie prior to the onset of clinical signs of the disease and the increase re ached 11 to 45 fold relative to uninfected controls in terminally ill mice. Spi 2, in common with four of the other scrapie responsive genes studied, is known to be associated with pro-inflammatory processes. These observatio ns underline the importance of cell reactivity in TSE, In addition, scrg2 m RNA the level of which is enhanced in TSE-infected mouse brain, was identif ied as a previously unrecognized long transcript of the murine aldolase C g ene. However, the level of the principal aldolase C mRNA is unaffected in T SE. The increased representation of the longer transcript in the late stage of the disease may reflect changes in mRNA processing and/or stability in reactive astrocytes or in damaged Purkinje cells. (C) 2000 Elsevier Science B.V. All rights reserved.