We hypothesize that bone morphogenetic protein-7 (BMP-7, osteogenic protein-1), a member of the TGF-beta superfamily which is produced most abundantly in the adult in kidney, plays a role in bone mineral homeostasis and/or renal function and structure. To further define the role of BMP-7 in kidney, we have developed mice for BMP-7 under the control of the mouse mammary tumor virus promoter (MMTV) which expresses in the collecting tubule and the phosphoenol pyruvate carboxykinae (PEPCK) promoter which expresses in the proximal tubule. We have developed mice transgenic for the MMTV promoter driving BMP-7 and for the PEPCK promoter driving BMP-7. In MMTV/BMP-7 transgenic mice, we have detected BMP-7 transgene RNA in the collecting tubule of kidney. There is no apparent renal or bone phenotype. We have bred these mice with MMTV/p53 mice, which overexpress p53 in the ureteric bud, the anlage of the collecting tubule. The ureteric bud shows reduced expression of BMP-7 and the mice have a defect in nephronogenesis, resulting in small kidneys, reduced glomerular numbers, and focal segmental glomerulosclerosis in the adult. Dual transgenic mice have partial normalization of kidney size and glomerular numbers. These findings show that expression of BMP-7 can rescue the p53-driven defect and add further evidence that BMP-7 is a critical factor in nephronogenesis
