Murine models of human genetic skeletal disorders

Genetic and molecular biological studies have recently resulted in the identification of gene mutations responsible for a large number of human osteochondrodysplasias, skeletal disorders associated with abnormalities of cartilage and/or bone development and growth. Mouse strains carrying mutations in homologous genes are useful, not only because they provide sources of abnormal tissue, but also because specific hypotheses concerning pathogenetic mechanisms can be readily tested. Many of the strains with abnormalities in cartilage and bone have been studied by morphological and biochemical methods for years without successful identification of the genes involved, but recent use of linkage mapping, followed by positional candidate gene cloning, has greatly improved the situation. In a number of instances, the mutations are now known. This is also true for the three "classical" mouse mutants chondrodysplasia (cho), disproportionate micromelia (Dmm) and cartilage matrix deficiency (cmd). In the three strains, mutations in alpha 1(XI) collagen, alpha 1(II) collagen or aggrecan lead to severe defects in the structure and function of cartilage with significant negative effects on longitudinal bone growth.