|Budget Amount *help
¥15,700,000 (Direct Cost: ¥15,700,000)
Fiscal Year 2002: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2001: ¥10,100,000 (Direct Cost: ¥10,100,000)
In our murine strain deficient in MT1-MMP gene expression, the bone morphogenesis was severely impaired, consistent with the past reports. Next question would be an address to know which cell lineages in bone tissue are responsible to work with expressing MT1-MMP during the bone morphogenesis under the physiologic state. To see if a recovering of the MT1-MMP limitedly in bone tissue helps to revart the phenotype, a conditional transgenic strain is under construction based on the knock-out mice, in which expression of MT1-MMP is recovered restrictedly in osteoblasts. On the other hand, MT1-MMP plays a important role in angiogenesis around the ossification center during the second ossification. In order to understand the role more profoundly, three-dimensional culture of muscle chunks in type-I collagen has been conducted. Angiogenesis through the collagen was observed during the culturing period. The angiogenesis was severely impaired with the mucle chunk of the MT1-MMP deficient strain
compared to the wild type or the hetero-zygote.
MT1-MMP in the new vessels was predominantly expressed in endothelial cells. Questions remains how MT1-MMP plays a role in angiogenesis, why other proteinases can not compensate the functions sufficiently, or whether the impairment in second ossification in MT1-MMP deficient mice is induced predominantly by the poor angiogenesis around the bone. The conditional transgenic mice could provide us with some hints to ask for the queries.
MT5-MMP has been found to expressed at neural cells such in cerebrum, cerebellum, and hypocampus. However, no distinct abnormality has been detected in a strain deficient in MT5-MMP gene. Based on the specificity in MT5-MMP expression, a neurite extension assay was performed with the murine neural cells derived from dorsal route ganglia, demonstrated that the protrusion of the neurite was facilitated on laminin, and inhibited on heparin binding proteoglycan. Adding a soluble MT5-MMP purified, The latter inhibition has released with a degradation of the substrate.
Immunohistochemically, endogenous MT5-MMP was detected predominantly at the growth cone.
MT4-MMP has been shown to be expressed such at a cortex in the frontal lobe of brain, hypocampus, cerebellum, nephron, smooth muscle cells in the vessels, heart, and red pulp in spleen. Histologically, no gloss abnormality was found in a strain- deficient in MT4-MMP gene. Several functional analyzes should be performed next to know how MT4-MMP plays roles in murine tissue. Less