Mammalian skeletogenesis and extracellular matrix: What can we learn from knockout mice?

Formation of the vertebrate skeleton and the proper functions of bony and c artilaginous elements are determined by extracellular, cell surface and int racellular molecules, Genetic and biochemical analyses of human heritable s keletal disorders as well as the generation of knockout mice provide useful tools to identify the key players of mammalian skeletogenesis, This review summarises our recent work with transgenic animals carrying ablated genes for cartilage extracellular matrix proteins, Some of these mice exhibit a l ethal phenotype associated with severe skeletal defects (type II collagen-n ull, perlecan-null), whereas others show mild (type IX collagen-null) or no skeletal abnormalities (matrilin-1-null, fibromudulin-null, tenascin-C-nul l), The appropriate human genetic disorders are discussed and contrasted wi th the knockout mice phenotypes.