PHENOTYPIC AND BIOCHEMICAL CONSEQUENCES OF COLLAGEN-X MUTATIONS IN MICE AND HUMANS

Skeletal biology has entered an exciting period with the technological advances in murine transgenesis and human genetics. This review focus es on how these two approaches are being used to address the role of c ollagen X, the major extracellular matrix component of the focal zone of endochondral ossification, the hypertrophic cartilage zone. The hyp othesized role of this unique collagen in skeletal morphogenesis and t he phenotypic and biochemical consequences resulting from the disrupti on of its function are discussed. Specifically, data from three murine models, including transgenic mice with a dominant interference phe no type for collagen X, and two sets of mice with an inactivated collagen X gene through gene targeting and homologous recombination, as well a s the human disorder of Schmid metaphyseal chondrodysplasia resulting from mutations in collagen X, are summarized and compared. Several inc onsistencies and unresolved issues regarding the murine and human phen otypes and the function of collagen X are discussed.