Cartilage Oligomeric Matrix Protein-Deficient Mice Have Normal Skeletal Development

Cartilage oligomeric matrix protein (COMP) belongs to the thrombospondin family and is a homopentamer primarily expressed in cartilage. Mutations in the COMP gene result in the autosomal dominant chondro-dysplasias pseudoachondroplasia (PSACH) and some types of multiple epiphyseal dysplasia (MED), which are characterized by mild to severe short-limb dwarfism and early-onset osteoarthritis. We have generated COMP-null mice to study the role of COMP in vivo. These mice show no anatomical, histological, or ultrastructural abnormalities and show none of the clinical signs of PSACH or MED. Northern blot analysis and immuno-histochemical analysis of cartilage indicate that the lack of COMP is not compensated for by any other member of the thrombospondin family. The results also show that the phenotype in PSACH/MED cartilage disorders is not caused by the reduced amount of COMP. Cartilage oligomeric matrix protein (COMP) is a member of the thrombospondin family of extracellular matrix proteins (1, 4, 30, 35). The protein consists of five 87-kDa subunits held together by interchain disulfide bonds (19), forming a 435-kDa pentameric protein. COMP is expressed in all types of cartilage (14, 19), vitreous of the eye (33), tendon (12, 38), and vascula