Phenotypic and biochemical consequences of collagen X mutations in mice and humans

Abstract

Skeletal biology has entered an exciting period with the technological advances in murine transgenesis and human genetics. This review focuses on how these two approaches are being used to address the role of collagen X, the major extracellular matrix component of the focal zone of endochondral ossification, the hypertrophic cartilage zone. The hypothesized role of this unique collagen in skeletal morphogenesis and the phenotypic and biochemical consequences resulting from the disruption of its function are discussed. Specifically, data from three murine models, including transgenic mice with a dominant interference phenotype for collagen X, and two sets of mice with an inactivated collagen X gene through gene targeting and homologous recombination, as well as the human disorder of Schmid metaphyseal chondrodysplasia resulting from mutations in collagen X, are summarized and compared. Several inconsistencies and unresolved issues regarding the murine and human phenotypes and the function of collagen X are discussed.