The TRPV5 promoter as a tool for generation of transgenic mouse models.

The transient receptor potential vanilloid 5 (TRPV5) is a Ca(2+) channel, which is expressed in renal late distal convoluted tubules (DCT2s) and connecting tubules (CNTs). These tubules play a major role in hormone controlled renal Ca(2+) reabsorption, and thereby in body Ca(2+) homeostasis, as well as urinary excretion of other electrolytes, including Na(+) and K(+). DCT2 and CNT are difficult to distinguish from the surrounding structures and thereby to study by direct functional methods. We developed a transgenic mouse model expressing enhanced green fluorescent protein (EGFP) driven by the TRPV5 promoter to identify these specific tubules. Expression of EGFP in the DCT2 and CNT allows the isolation of pure DCT2 and CNT populations for proteomic and physiological analyses. The TRPV5 promoter is also useful for generating conditional knockout mouse models in a cell-specific manner. TRPV5 promoter driven Cre recombinase expression will be useful for inducing DCT2 and CNT specific gene silencing of various channels, pumps, carriers, and receptors. In this chapter, we describe the strategy for developing transgenic mouse lines involving the TRPV5 promoter, provide a description of extensive validation of these mouse lines, and discuss possible uses and limitations.