Spondylometaphyseal dysplasia in mice carrying a dominant negative mutation in a matrix protein specific for cartilage-to-bone transition.

The vertebrate skeleton is formed primarily by endochondral ossification, starting during embryogenesis when cartilage anlagens develop central regions of hypertrophic cartilage which are replaced by bony trabeculae and bone marrow. During this process chondrocytes express a unique matrix molecule, type X collagen. We report here that mice carrying a mutated collagen X transgene develop skeletal deformities including compression of hypertrophic growth plate cartilage and a decrease in newly formed bone, as well as leukocyte deficiency in bone marrow, reduction in size of thymus and spleen, and lymphopenia. The defects indicate that collagen X is required for normal skeletal morphogenesis and suggest that mutations in COL10A1 are responsible for certain human chondrodysplasias, such as spondylometaphyseal dysplasias and metaphyseal chondrodysplasias.