Nondecalcified histologic sections of the tibia of 1-week-old (a) CasR-deficient, and (b) CasR- and Gcm2-deficient mice. Double knockout reverses the mineralization defect observed in CasR^–/– mice. This result indicates that an excess of PTH may somehow directly produce a picture of rickets and osteomalacia and that this abnormality is not due to the absence of CaSR in bone cells. It will be important to find out what very high PTH levels might be doing to the proteins and transport systems that regulate mineralization in these mice.