Drosophila melanogaster: a simple genetic model of kidney structure, function and disease.

Abstract

Although the genetic basis of many kidney diseases is being rapidly elucidated, their experimental study remains problematic owing to the lack of suitable models. The fruitfly Drosophila melanogaster provides a rapid, ethical and cost-effective model system of the kidney. The unique advantages of D. melanogaster include ease and low cost of maintenance, comprehensive availability of genetic mutants and powerful transgenic technologies, and less onerous regulation, as compared with mammalian systems. Renal and excretory functions in D. melanogaster reside in three main tissues - the transporting renal (Malpighian) tubules, the reabsorptive hindgut and the endocytic nephrocytes. Tubules contain multiple cell types and regions and generate a primary urine by transcellular transport rather than filtration, which is then subjected to selective reabsorption in the hindgut. By contrast, the nephrocytes are specialized for uptake of macromolecules and equipped with a filtering slit diaphragm resembling that of podocytes. Many genes with key roles in the human kidney have D. melanogaster orthologues that are enriched and functionally relevant in fly renal tissues. This similarity has allowed investigations of epithelial transport, kidney stone formation and podocyte and proximal tubule function. Furthermore, a range of unique quantitative phenotypes are available to measure function in both wild type and disease-modelling flies.