Establishment of an MT4‐MMP‐deficient mouse strain representing an efficient tracking system for MT4‐MMP/MMP‐17 expression <i>in vivo</i> using β‐galactosidase

Abstract

The biological functions of membrane‐type 4 matrix metalloproteinase (MT4‐MMP/MMP‐17) are poorly understood because of the lack of a sensitive system for tracking its expression in vivo . We established a mutant mouse strain ( Mt4‐mmp −/– ) in which Mt4‐mmp was replaced with a reporter gene encoding β‐galactosidase (LacZ). Mt4‐mmp −/– mice had normal gestations, and no apparent defects in growth, life span and fertility. Using LacZ as a marker, we were able to monitor the expression and promoter activity of Mt4‐mmp for the first time in vivo . The tissue distribution of Mt4‐mmp mRNA correlated with LacZ expression, and we showed that Mt4‐mmp is expressed primarily in cerebrum, lung, spleen, intestine and uterus. We identified LacZ‐positive neurons in the cerebrum, smooth muscle cells in the intestine and uterus, and macrophages located in the lung alveolar or intraperitoneal space. Contrary to the reported role of MT4‐MMP as a tumor necrosis factor‐α (TNF‐α) sheddase, the lipopolysaccharide (LPS)‐induced release of TNF‐α from Mt4‐mmp −/– macrophages was similar to that in wild‐type cells, and expression of Mt4‐mmp mRNA was repressed following LPS stimulation. Thus, we have established a mutant mouse strain for analyzing the physiological functions of MT4‐MMP, which also serves as a sensitive system for monitoring and tracking the expression of MT4‐MMP in vivo .