2011), we produced conclusive data that without ClC-3 and ClC-5, osteoblasts cannot mineralize in vitro. It is likely that for further in vivo studies, cell-specific knockouts may be required; mutations of Clcn5 cause Dent’s disease (Silva et al. 2003) and constitutive Clcn3/Clcn5 double knockout animals might be lethal if the expected severe skeletal mineralization defect occurs. This evidence concerns the gene CLCN5 and Dent disease.