STRUCTURAL ORGANIZATION AND CHROMOSOMAL LOCALIZATION OF THE MOUSE COLLAGENASE TYPE-I GENE

A clone containing genomic sequences of part of the murine collagenase type 1 (MMP-1) gene was isolated. It contains exons 1-6 encoding all the domains required for collagenase function and 9 kb of 5'-flanking sequences. The gene organization and exon/intron borders are highly similar to the already described human and rabbit MMP-1 genes. However, neither the intron sequences, nor the promoter region up to position -660 exhibit significant sequence homologies with rabbit and human MMP-1, except for an AP-1-binding site and two PEA-3 consensus sequences. Binding studies in vitro revealed that the AP-1-binding site is recognized by Fos/Jun heterodimers with very high affinity. By in situ hybridization the mouse MMP-1 gene was located to the A1-A2 region of chromosome 9 in proximity to the curly whiskers (cw) locus. Based on the lack of sequence homologies of the promoter and intron regions, and since the chromosomal localization of the mouse and human MMP-1 genes may not be syntenic, these data strongly support previous suggestions that the MMP-1 genes from mouse, compared with rabbit and human, have evolved from different ancestoral genes. The presence of the AP-1- and PEA-3- binding sites in all mammalian MMP-1 genes isolated so far, may, however, suggest evolutionary selection for common regulatory mechanisms of MMP-1 transcription.