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The Extracellular Calcium-Sensing Receptor (CaSR) Is a Critical Modulator of Skeletal Development

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Sci. Signal.  02 Sep 2008:
Vol. 1, Issue 35, pp. ra1
DOI: 10.1126/scisignal.1159945

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Bone Censor

The extracellular calcium-sensing receptor (CaSR) is a guanine nucleotide-binding protein (G protein)–coupled receptor (GPCR) that responds to changes in the concentration of extracellular calcium ([Ca2+]e) and modulates various functions of parathyroid cells (PTCs), chondrocytes (the cells that produce cartilage), osteoblasts, and renal tubular cells. Previous attempts to characterize the CaSR in Casr−/− mice have been hampered by the expression of an alternatively spliced form of the receptor that provides at least partial compensation for loss of the full-length receptor (see the Perspective by Brown and Lian). Chang et al. have now developed mice with cell type–specific knockout of Casr that do not express the alternative receptor. Mice with PTC- or osteoblast-specific deletion of Casr were viable but had postnatal skeletal defects. Unexpectedly, knockout of Casr in chondrocytes was lethal. Mice in which chondrocyte-specific knockout of Casr was induced late in embryonic life were viable but had delayed growth plate development. Together, these findings reveal a previously unappreciated role for the CaSR in embryonic and postnatal skeletal development.