Murine Matrix Metalloproteinase 9 Gene

• Published in: The Journal of biological chemistry 1999-02, Vol.274 (9), p.5588-5596
• Main Authors: Munaut, Carine, Salonurmi, Tuire, Kontusaari, Sirpa, Reponen, Paula, Morita, Takako, Foidart, Jean-Michel, Tryggvason, Karl
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.9.5588

Knowledge about the regulation of cell lineage-specific expression of extracellular matrix metalloproteinases is limited. In the present work, the murine matrix metalloproteinase 9 (MMP-9) gene was shown to contain 13 exons, and the 2.8-kilobase pair upstream region was found to contain several common promoter elements including a TATA box-like motif, three GC boxes, four AP-1-like binding sites, an AP-2 site, and three PEA3 consensus sequences that may be important for basic activity of the gene. In order to identify cell-specific regulatory elements, constructs containing varying lengths of the upstream region in front of a LacZ reporter gene were made and studied for expression in transgenic mice generated by microinjection into fertilized oocytes. Analyses of the mice revealed that the presence of sequences between −2722 and −7745 allowed for expression in osteoclasts and migrating keratinocytes, i.e. cells that have been shown to normally express the enzyme in vivo . The results represent the first in vivo demonstration of the location of cell-specific control elements in a matrix metalloproteinase gene and show that element(s) regulating most cell-specific activities of 92-kDa type collagenase are located in the −2722 to −7745 base pair region.