Previous studies failed to find a direct role for CaR in mice homozygous for targeted disruption of exon 5 of the CaR gene, which encodes a segment of the extracellular domain of this receptor.(14,15) These observations may have been confounded by the severe hyperparathyroidism and accompanying hypercalcemia and hypophosphatemia in this animal model. This evidence concerns the gene CASR and hypophosphatemia.