TRANSGENIC MODELS IN RENAL TUBULAR PHYSIOLOGY

Animal transgenesis has proven to be useful for physiological as well as physiopathological studies. Besides the classical approach based on the random integration of a DNA construct in the mouse genome, gene t argeting can be achieved using totipotent embryonic stem (ES) cells fo r targeted transgenesis. Transgenic mice are then derived from the tra nsgenic ES cells. This allows the introduction of null mutations in th e genome (so-called knock-out) or the control of the transgene express ion by the endogenous regulatory sequences of the gene of interest (so -called knock-in). Development of these transgenic animals leads to a better understanding of the cellular function of many genes or to the generation of animal models for human diseases. The purpose of this sh ort review is to describe animal models in renal tubular physiopatholo gy. Recent progresses will allow the generation of animal models with conditional expression of the transgene of interest or with a conditio nal gene mutation. This permits spatial and temporal control of the ex pression of the transgene or of the mutation. This should allow the ge neration of models suitable for physiological analysis or closer to di sease state.