The development of the mammalian kidney is a very complex process, involving branching morphogenesis of the ureter and the formation of nepherons. Once the nepheron is formed, the next stage of development is for the loop of Henle and collecting duct to elongate into renal pelvis, forming the medulla. Little is known about this elongation phase of development in the kidney. Failed elongation of renal tubules causes congenital renal displasia as seen in patients with Beckwith-Wiedemann syndrome (BWS). Our research into the cell cycle regulation and development has identified p57, a cyclin-dependent kinase inhibitor and thus a negative cell cycle regulator, as one of the genes responsible for BWS and demonstrated that it is indispensable for the elongation of renal tubules. Mice deficient in the p57 function form defective kidney medullae containing fewer numbers of renal tubules. Our long-term objectives are to elucidate the role of p57KIP2 in the development of the kidney. This proposal seeks funding for developing an alternative technology to generate mice deficient in specific gene functions in the kidney. This technology should produce mutant mice at a fraction of the cost and time associated with conventional knockout. With this technology, we would be able to study the function of genes identified in our large scale gene discovery screening (covered by another grant application) in a high throughput manner, leading to a better understanding of the development and the disease mechanisms of the kidney. Furthermore, the technology will benefit the kidney research community as a whole.