COORDINATE EXPRESSION OF MATRIX METALLOPROTEINASE FAMILY MEMBERS IN THE UTERUS OF NORMAL, MATRILYSIN-DEFICIENT, AND STROMELYSIN-1-DEFICIENTMICE

The expression patterns of matrix metalloproteinase (MMP) family membe rs during the murine estrous cycle and postpartum uterine involution w ere analyzed, and the consequence of removing specific MMPs during ute rine functions was determined using mice deficient in either matrilysi n (MAT) or stromelysin-1 (STR-1). in wild-type animals, MAT, STR-1, ST R-2, STR-3, and gelatinase A were consistently expressed during the mo st active phases of the estrous cycle, estrus and proestrus. The messe nger RNA for these MMPs as well as collagenase-3 and the tissue inhibi tors of metalloproteinases were also expressed during uterine involuti on, as determined by Northern analysis and in situ hybridization. Nota bly, MAT, STR-2, and collagenase-3 messenger RNA levels were elevated at early times of involution and rapidly decreased with time, whereas the transcripts for other MMPs remained elevated throughout the involu tion process. Involution proceeded normally in mice lacking MAT or STR -1; however, the expression of STR-1 and STR-2 was dramatically up-reg ulated in MAT nullizygous mice, and the expression of MAT and STR-2 wa s moderately up-regulated in STR-1-deficient animals. We conclude that the concerted action of several MMPs is likely to play an important r ole in the remodeling of the postpartum uterus, and that mechanisms th at compensate for the loss of a specific MMP during this process appea r to exist.