Short Limbs, Cleft Palate, and Delayed Formation of Flat Proliferative Chondrocytes in Mice with Targeted Disruption of a Putative Protein Kinase Gene, Pkdcc (AW548124)

During long bone development, round proliferative chondrocytes (RPCs) differentiate into flat proliferative chondrocytes (FPCs), and then into hypertrophic chondrocytes (HCs). FPCs and HCs support longitudinal bone growth. Here we show that a putative protein kinase gene, Pkdcc (AW548124), is required for longitudinal bone growth. We originally found Pkdcc expressed in the head organizer, but it is also expressed throughout embryogenesis and in various adult tissues. Pkdcc-/- embryos had no head organizer-related defects, but showed various morphological abnormalities at birth, including short limbs, cleft palate, sternal dysraphia, and shortened intestine. In the long bones of the limbs, only the mineralized regions were shortened, and the cartilage length was normal. In the humerus, Pkdcc was strongly expressed in the early FPCs, and FPC and HC formation was delayed in Pkdcc-/- mutants. Together, these data indicate that Pkdcc encodes a protein kinase that is required for the appropriate timing of FPC differentiation.