The Matrix Metalloproteinase-14 (MMP-14) Gene Is Structurally Distinct from Other MMP Genes and Is Co-expressed with the TIMP-2 Gene during Mouse Embryogenesis

Abstract

The matrix metalloproteinases (MMPs) are a family of zinc-containing matrix degrading endopeptidases. A subfamily of membrane type (MT) -MMPs has been de- scribed recently. We have determined the structure of the gene (Mmp14) encoding the first MT-MMP to be de scribed, MT1-MMP (MMP-14), and mapped it to mouse chromosome 14. The mouse MMP-14 protein is encoded by ten exons. The novel C-terminal peptide domains of MMP-14 are encoded by a single large exon that also encodes the 3'-untranslated region. The structure of the exons encoding the catalytic domain and pro-domain of MMP-14 is distinct from previously described MMP genes, whereas the exons encoding the hemopexin-like domains are similar to those of most other MMP genes. Mmp14 and the gene for tissue inhibitor of metalloproteinases-2 (Timp2) show a temporally and spatially co- regulated expression during mouse development. They are co-expressed during vascular and urogenital development and during the development of osteocartilaginous and musculotendinous structures. The stringent co-expression of these two genes suggests common regulatory pathways that may have important functional implications for the activation of pro-gelatinase A in health and disease.