YOSHIKI Atsushi RIKEN,Division of Experimental Animal Research, Research Scientist, 実験動物室, 研究員 (40212310)
IKE Fumio RIKEN,Division of Experimental Animal Research, Senior Research Scientist, 実験動物室, 先任研究員 (40183157)
平岩 典子 理化学研究所, 実験動物室, 先任技師 (30200380)
|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1998 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1997 : ¥2,600,000 (Direct Cost : ¥2,600,000)
Mice without the gene for tenascin-C, a multifunctional extracellular matrix protein expressed in many important biological events, including wound healing, did not show any phenotype. However, it is now obvious that the phenotype of deletion of one gene frequently depends on the genetic background. Therefore, we have newly generated tenascin-C knockout mice(KO)by backcrossing original KO into three congenic lines : C57BL/6N, BALB/cA, and GRS/A (GR). And we investigated the disease course of reversible kidney injury, Habu-snake venom-induced proliferative glomerulonephritis. In all strains, the disease was more severe in KO, but the severity varied with the strain. The KO-GR showed abnormal regenerative reactions, including reduced proliferation of mesangial cells, key players in glomerulonephritis, and reduced production of some kinds of cytokines and matrices, leading to poor formation of granulation tissue. In culture, the mesangial cells from the KO-GR had the same potential for proliferation and response to cytokines as controls, but interestingly, to achieve this potential, they required contact with tenascin-C.These reactions were blocked by an anti-tenascin monoclonal antibody. The results of the present study, the first report showing the most dramatic phenotype so far discovered, have strongly suggested the importance of tenascin-C in the resolution of the renal inflammation and that of the genetic background on which the KO was developed.