A MOUSE MODEL OF HUMAN FAMILIAL HYPOCALCIURIC HYPERCALCEMIA AND NEONATAL SEVERE HYPERPARATHYROIDISM

Mice lacking the calcium-sensing receptor (Casr) were created to exami ne the receptor's role in calcium homeostasis and to elucidate the mec hanism by which inherited human Casr gene defects cause diseases. Casr (+/-) mice, analogous to humans with familial hypocalciuric hypercalce mia, had benign and modest elevations of serum calcium, magnesium and parathyroid hormone levels as well as hypocalciuria. In contrast, Casr (-/-) mice, like humans with neonatal severe hyperparathyroidism, had markedly elevated serum calcium and parathyroid hormone levels, parath yroid hyperplasia, bone abnormalities, retarded growth and premature d eath. Our findings suggest that Casr mutations cause these human disor ders by reducing the number of functional receptor molecules on the ce ll surface.