title: A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.
abstract: Mice lacking the calcium-sensing receptor (Casr) were created to examine the receptor's role in calcium homeostasis and to elucidate the mechanism by which inherited human Casr gene defects cause diseases. Casr+/- mice, analogous to humans with familial hypocalciuric hypercalcemia, 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, parathyroid hyperplasia, bone abnormalities, retarded growth and premature death. Our findings suggest that Casr mutations cause these human disorders by reducing the number of functional receptor molecules on the cell surface.
mesh_terms: D000818:Animals; D001848:Bone Diseases, Developmental / Q000235:genetics; D002118:Calcium / Q000097:blood / Q000652:urine; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D006579:Heterozygote; D006706:Homeostasis; D006720:Homozygote; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics* / Q000378:metabolism*; D006961:Hyperparathyroidism / Q000235:genetics* / Q000378:metabolism*; D006965:Hyperplasia; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010280:Parathyroid Glands / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood
chemical_list: D002135:Calcium-Binding Proteins; D010281:Parathyroid Hormone; D002118:Calcium