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Vol. 9, Issue 2, 421-435, February 1998
and
*Department of Cell Biology, Vanderbilt University, Nashville,
Tennessee 37232; and
To examine the role of matrilysin (MAT), an epithelial
cell-specific matrix metalloproteinase, in the normal development and function of reproductive tissues, we generated transgenic animals that
overexpress MAT in several reproductive organs. Three distinct forms of
human MAT (wild-type, active, and inactive) were placed under the
control of the murine mammary tumor virus promoter/enhancer. Although
wild-type, active, and inactive forms of the human MAT protein could be
produced in an in vitro culture system, mutations of the MAT cDNA
significantly decreased the efficiency with which the MAT protein was
produced in vivo. Therefore, animals carrying the wild-type MAT
transgene that expressed high levels of human MAT in vivo were further
examined. Mammary glands from female transgenic animals were
morphologically normal throughout mammary development, but displayed an
increased ability to produce Roche Bioscience, Palo Alto,
California 94304
-casein protein in virgin animals. In
addition, beginning at approximately 8 mo of age, the testes of male
transgenic animals became disorganized with apparent disintegration of
interstitial tissue that normally surrounds the seminiferous tubules.
The disruption of testis morphology was concurrent with the onset of
infertility. These results suggest that overexpression of the
matrix-degrading enzyme MAT alters the integrity of the extracellular
matrix and thereby induces cellular differentiation and cellular
destruction in a tissue-specific manner.
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