To understand the role of the calcium-sensing receptor (CasR) in the skeleton, the inventor used a genetic approach to remove the confounding effects of elevated parathyroid hormone (PTH) in CasR-deficient mice. Mice with a deficiency of glial cells missing 2 (Gcm2) lack parathyroid glands, but exhibit mild hypoparathyroidism, as well as normal skeletal growth and development. In this technology, CasR- and Gcm2-deficient mice were intercrossed. The Gcm2 deficiency rescued the perinatal lethality in CasR-deficient mice. In addition, the CasR- and Gcm2-deficient mice demonstrated healing of the abnormal mineralization of cartilage and bone associated with CasR deficiency, indicating that rickets and osteomalacia in CasR-deficient mice are not due to an independent function of CasR in bone and cartilage, but to the effect of severe hyperparathyroidism in the neonate. Analysis of the skeleton of 6-week-old CasR- and Gcm2-deficient mice also failed to identify any essential, nonredundant role for CasR in regulating chondrogenesis or osteogenesis, but further studies are needed to establish the function of CasR in the skeleton. In contrast, Gcm2 and CasR deficiency failed to rescue the hypocalciuria in CasR-deficient mice, consistent with direct regulation of urinary calcium excretion by CasR in the kidney. Gcm2- and CasR-deficient mice provide an important model for evaluating the extraparathyroid functions of CasR.

This mouse model can be used to test the effects of CasR in bone amd cartilage, as well as its role in regulating physiological functions without the confounding effects of excess PTH.

File Number: 06KUMC017 

Other Information: *State of Development* Available for exclusive and non-exclusive license *Testing* Mouse Model Available