A New Transgenic Approach for the Kidney
Principal Investigator: Pumin Zhang
Abstract: 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.
Funding Period: 2003-08-05 - 2006-07-31
more information: NIH RePORT
- A transgenic approach for RNA interference-based genetic screening in miceShaohua Peng
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
Proc Natl Acad Sci U S A 103:2252-6. 2006..In a small-scale screening for developmental defects in the kidney, we uncovered a potential role of Id4 in the formation of the renal medulla. Our results demonstrate the feasibility of using RNAi for genetic screening in mice...
- Transgenic RNA interference in miceXue Gao
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA
Physiology (Bethesda) 22:161-6. 2007..Transgenic RNAi not only allows the study of biological processes not present in cultured cells but also offers chronic therapeutic potentials. In this review, we will summarize the developments in the generation of transgenic RNAi mice...
- Transgenic RNA interference in micePumin Zhang
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA
Methods Mol Biol 442:259-66. 2008..Furthermore, the knockdown effect can be transmitted through the germline in these animals. We describe a method of generating a transgenic RNAi mouse line...