Kidney-specific gene targeting: insight into thiazolidinedione-induced fluid retention

Conditional gene targeting technique, which is based on the use of Cre-loxP or Flp/FRT systems, has been increasingly used to study gene function of a particular cell type in vivo. The introduction of this technique to the kidney field is relatively recent but has already provided important insights into physiological or pathological functions of a number of genes in the kidney. This technique has recently been used to inactivate the peroxisome proliferator-activated receptor subtype gamma in the collecting duct, which leads to remarkable blockade of body weight gains and plasma volume expansion associated with thiazolidinediones. This finding not only helps understand pharmacology of the novel class of antidiabetic drugs, but also uncovers an important role of peroxisome proliferator-activated receptor subtype gamma in regulation of distal nephron fluid reabsorption. The present review represents an example for the use of the modern technique to address complex clinical problems. It is anticipated that over next few years this technique will be used by an increasing number of investigators for studying gene function in the kidney.