Genetic-Engineered Models of Skeletal Diseases I: Collagen Type X

Formation of the vertebrate skeleton is an intricately orchestrated, multistep process. Mechanisms underlying skeletogenesis need to account for the global specification of skeletal pattern, commitment of cells to skeletal and hematopoietic lineages, local control of skeletal shape and growth, as well as function and homeostasis of the skeletal tissue. The complexity of these processes is reflected by the large number of diseases with skeletal manifestations. Specifically, osteochondrodysplasias, defined as developmental disorders affecting cartilage and/or bone, comprise a diverse group of more than 150 characterized forms of skeletal abnormalities (1 ). Whereas the intricacies of the processes underlying skeletogenesis are still not fully understood, the recent identification of the genetic basis for a number of heritable skeletal disorders is yielding significant insights (2 –4 ). To a large extent, these successes are because of the convergence of information gained from murine transgenesis, and from murine and human genetics.