Regulation of TIMP gene expression in cell culture and during mouse embryogenesis.

We have identified elements in the 5' region of the murine tissue inhibitor of metalloproteinase (TIMP) gene which control the response to serum, phorbol esters and transforming growth factor beta (TGF-beta) in cell culture. These elements lie between -858 and -601 relative to the translation initiation start site in the gene and are distinct from those that control expression in response to virus induction. The temporal and spatial expression of the TIMP gene was also analysed during mouse embryogenesis using in situ hybridization. A transgenic mouse line was constructed which expressed a TIMP/lac Z fusion gene. Using in situ beta-galactosidase assays we were able to compare the expression of the transgene with the endogenous gene. Thus we concluded that most of the sequences controlling in vivo expression of TIMP were present in the transgene and could be localised to the 5' region of the gene.