GELATINASE-B LACZ TRANSGENIC MICE, A MODEL FOR MAPPING GELATINASE B EXPRESSION DURING DEVELOPMENTAL AND INJURY RELATED TISSUE REMODELING/

Matrix metalloproteinases (MMPs) drive normal tissue remodeling and ar e implicated in a wide range of pathologies, Although MMP activity is controlled at multiple levels, the primary regulation of MMP activity is transcriptional. The transcriptional promoter elements required for MMP gene expression in cultured cells have been defined, but this has not been extended to the in vivo situation. In this paper, we show th at the DNA sequences between -522 and +19 of the rabbit gelatinase B g ene (MMP-9) (as characterized in the transgenic mouse line 3445) const itute a minimal promoter that drives appropriate developmental and inj ury-induced reporter gene expression in transgenic mice. We further sh ow that the expression and activity of three transcription factors (NF -kappa B, AP-2, and Sp1) that control the activity of the gelatinase B promoter are selectively induced in the epithelium migrating to heal a wound. Although promoter activity parallels expression of the endoge nous gene in cell cultures, we show by several criteria that cell cult ures cannot model many aspects of promoter regulation in vivo. This st udy reveals that the transgenic mouse line 3445 might be a useful mode l for investigating the regulation of gelatinase B expression in vivo and for identifying and characterizing new drugs that can control gela tinase B gene transcription.