PTH PTHRP RECEPTOR IN EARLY DEVELOPMENT AND INDIAN HEDGEHOG-REGULATEDBONE-GROWTH/

The PTH/PTHrP receptor binds to two ligands with distinct functions: t he calcium-regulating hormone, parathyroid hormone (PTH), and the para crine factor, PTH-related protein (PTHrP). Each ligand, in turn, is li kely to activate more than one receptor. The functions of the PTH/PTHr P receptor were investigated by deletion of the murine gene by homolog ous recombination. Most PTH/PTHrP receptor (-/-) mutant mice died in m id-gestation, a phenotype not observed in PTHrP (-/-) mice, perhaps be cause of the effects of maternal PTHrP. Mice that survived exhibited a ccelerated differentiation of chondrocytes in bone, and their bones, g rown in explant culture, were resistant to the effects of PTHrP and So nic hedgehog. These results suggest that the PTH/PTHrP receptor mediat es the effects of Indian Hedgehog and PTHrP on chondrocyte differentia tion.