ABSTRACT Animal modeling of disease states and bioreporters for in situ analysis of cellular dynamics are an essential aspect of kidney, urological and hematopoietic research; however, most studies focus on genetic manipulation within the whole organism or kidney specific cell types, which does not accurately reflect disease states that are often associated with defects in individual cells or groups of cells. This discrepancy is largely due to the technical chal- lenges of being able to unrestrictedly induce Cre recombination in an optically selected group of cells within an intact organism. Therefore, we believe that a system for controlled genetic manipulation (resulting in loss of function alleles or expression of exogenous cDNAs/bioreporters) within a group of cells of a viable organism is required. This system should not alter or perturb the surrounding environment and should allow for potential systems based analysis and biomarker incorporation. Therefore, we hypothesize that transgenic lines ubiqui- tously expressing a light inducible Cre would allow for such unseen optical spatial and temporal control within a living organism. This Light Inducible Recombination (LIR) systems will be established within both the mouse and the zebrafish model organisms. Upon completion of this proposal we will have established versatile and efficient tools for selective genetic alterations that will facilitate regional and potentially single cell analysis in a multitude of research fields. We anticipate that this research will have a broad positive impact on a number areas of kidney, urological and hematopoietic research.

Multiple renal, urological and hematopoietic diseases are derived from genetic alterations or accumulation of biochemical alterations in a single or a cluster of cells. We are proposing to generate a genetic tool to allow for regional and potentially single cell genetic alterations with spatial and temporal control. This tool will allow for better understanding of disease progression which is essential for disease prevention.