The PTH/PTHrP receptor in Jansen's metaphyseal chondrodysplasia.

JMC is a rare autosomal dominant form of short limb dwarfism characterized by asymptomatic hypercalcemia and skeletal deformities, despite low PTH and PTHrP levels. This rare disorder is likely to be caused by activating mutations in the PTH/PTHrP receptor leading to ligand-independent cAMP accumulation. The analysis of genetically altered mice which lack either PTHrP or the PTH/PTHrP receptor, as well as of transgenic mice in which the mutant receptor is targeted to the growth plate, has provided a molecular explanation for the severe skeletal abnormalities seen in JMC. In addition, the study of this rare human disorder has further elucidated the fundamental role played by the PTH/PTHrP receptor in mediating both the paracrine/autocrine actions of PTHrP in growth plate development and bone elongation, as well as the endocrine actions of PTH. The insight gained from the study of this human disease model is likely to continue to provide an important tool to define the cellular and molecular mechanisms that mediate the biological roles of the PTH, PTHrP and their receptor.