CLONING AND DEVELOPMENTAL EXPRESSION OF A MEMBRANE-TYPE MATRIX METALLOPROTEINASE FROM CHICKEN

We have cloned a novel matrix metalloproteinase (MMP) from cultured ch icken embryo fibroblasts. The cDNA-derived protein sequence contains 6 08 amino acids including a C-terminal hydrophobic transmembrane domain of 24 amino acids and a cytoplasmic domain of 20 amino acids. This ch icken MMP is 72% similar to a recently described membrane-type MMP (MT -MMP) from human placenta (Sato, H., Takino, T., Okada, Y., Cao, J., S hinagawa, A., Yamamoto, E., and Seiki, M. (1994) Nature 370, 61-65). A ccordingly, we name this novel MMP chicken MT-MMP. As shown by Norther n blotting, two MT-MMP mRNAs of 6 and 10 kilobases are constitutively expressed but only modestly regulated by growth factors and cytokines in cultured chicken embryo fibroblasts. Both mRNAs are abundant in the head and body of 8- and 9-day-old chicken embryos. As shown by in sit u mRNA hybridization, MT-MMP is expressed in embryonic neural tube, sp inal ganglia, and respiratory epithelium, as web as in developing cart ilage and muscle. Using reverse transcription-polymerase chain reactio n, we have found MT-MMP mRNA in a-day-old chicken embryos and extraemb ryonic membranes. In addition, a strong correlation was observed betwe en the mRNA expression of MT-MMP and 72-kDa type IV collagenase. Colle ctively, the early MT-MMP mRNA expression and its co-localization in s everal tissues with 72-kDa type IV collagenase mRNA suggest that the M T-MMP plays an important role in early development.