Transgenic mouse models in studies of skeletal disorders.

Studies of mutations in mice and humans are identifying molecular defects in a number of osteochondrodysplasias. Disruption of collagen IX function in mice using 3 transgenic approaches causes a degenerative joint disease resembling osteoarthritis (OA). Mapping of a multiple epiphyseal dysplasia locus to the chromosomal region of COL9A2 suggests that certain heritable forms of OA in humans are also associated with collagen IX mutations. Colocalization of a murine chondrodysplasia, cho, with the Col11a1 locus, as well as mapping of the Stickler syndrome locus to COL11A2, implicate collagen XI genes as other candidates in heritable chondrodysplasias. The murine models permit exploration of pathogenetic mechanisms and testing of novel therapies.