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 si milar 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 recogn ized by Fos/Jun heterodimers with very high affinity. By in situ hybri dization the mouse MMP-1 gene was located to the A1-A2 region of chrom osome 9 in proximity to the curly whiskers (cw) locus. Based on the la ck of sequence homologies of the promoter and intron regions, and sinc e 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 evol ved 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, h owever, suggest evolutionary selection for common regulatory mechanism s of MMP-1 transcription.