Tg(Gfap-TNF*)K21Gkl

The -2663 to +93 region of the murine Gfap promoter, which has been shown to contain cis-regulatory elements required for astrocyte-specific expression was fused to human TNF genomic sequences containing a deletion mutation of the codons encoding the 1st to the 12th amino acids of the mature 17-kDa TNF protein. This mutant TNF gene has previously been shown to produce a transmembrane TNF protein that remains bioactive against cellular targets in vitro and in vivo. The genomic DNA was then ligated to the 0.77-kb EcoRI-Sal1 fragment containing the 3' UTR and polyadenylation site of the beta-globin gene, which replaces TNF 3' UTR sequences, thought to negatively regulate mRNA stability and translational efficiency. In this transgenic line, exogenous TNF protein production could be demonstrated by positive irnmunostaining of astrocytes in the spinal cord and brain sections using a polyclonal anti-human TNF Ab. (J:128072)