Targeted Gene Disruption in the Development of Mouse Models to Elucidate the Role of Receptor Guanylyl Cyclase Signaling Pathways in Physiological Function

The physiological role of receptor guanylyl cyclases (GCs), which transduce a signal via the generation of intracellular cyclic GMP, has been somewhat speculative since there are few specific inhibitors that discriminate among various receptor isoforms. Although the natriuretic peptide receptors have been thought to regulate cardiovascular and renal function, the exact contribution of the receptor subtypes has not been clarified. The normal role of the heat-stable enterotoxin receptor guanylyl cyclase remains undefined, and several orphan members of the family await the identification of ligands as well as function. Targeted gene disruption, familiarly known as gene knockout, has emerged during the past decade as a powerful technique for probing the function of gene products, and has been used to develop animal models of inherited human diseases. We are just beginning to apply gene targeting technology to the guanylyl cyclase receptor family. Reviewed here is the information gained to date from the targeted disruption of several members of the guanylyl cyclase receptor family, their ligands, or effector molecules.