A genetic approach for studying the role of thromboxane A2 in the kidney

Thromboxane A2 (TxA2) has been implicated in a number of processes in normal kidney physiology and as a mechanism for injury in renal disease. TxA2 is a biologically active derivative of arachidonic acid and has potent vasoconstrictive and platelet-activation functions. Its actions are mediated by binding to specific G-protein-associated receptors designated TP receptors. There are at least two isoforms of the human TP receptor, and pharmacological evidence suggests TP receptor heterogeneity in other species. TP receptors are located in the renal cortex, and there may also be TxA2 binding sites in the medulla. TP receptors are involved in some normal functions of the kidney, and there is considerable evidence that TP receptors may mediate renal damage in disease states. To assess directly the role of the TxA2 in normal kidney function and in murine models of human disease, we have used gene targeting to eliminate expression of the TP receptor in mice.