Role of Bone Morphogenetic Protein on the development of the Glomerulus

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Our previous studies on Bmp4 heterozygous mutants (Bmp4 +/-) suggest that BMP4 may have a role not only for the earlier development of kidney and urinary tract, but for the morphogensis of glomerulus. In the present study, we have developed mutant mice (neph-nog Tg) in which noggin, an endogenous inhibitor for BMP4, is over-expressed only in the glomerular epithelial cells using 5.4-kb 5'-franking region of the nephrin gene. In situ hybridization for noggin mRNA showed the signal is seen only in the glomerular epithelial cells. The expression level varies in different neph-nog Tgs, whereas no appreciable signal is seen in the wild type mice. The mice carrying higher level of noggin expression showed immature glomerular tuft surrounded by enlarged Bowman's capusule, the phenotype similar to that seen in Bmp4 +/-. Analyses of the P0 and E16.5 mutant embryos revealed that the initial defect is seen in the formation of the glomerular tuft. Whereas the differentiation and morphogenesis of glomerular epithelial cell layer per se is not affected, the glomerulus lacks the mesangial cells, resulting in the formation of glomerular microanuerysm. These results indicates that BMP4 is essential for the development of glomerular tuft