Structural and associative properties of cartilage matrix constituents in mice with hereditary chondrodysplasia.

The disarray of proliferative chondrocytes in epiphyses of cho/cho mice has been attributed to a defect in the extracellular matrix. Histochemically and ultrastructurally the matrix gives the appearance that it lacks the necessary structural integrity to guide proliferating cells into columns essential to elongation of endochondral bones. A study of rib cartilage was conducted to determine if the abnormality might be due to a defect in structural or associative properties of either of the two major matrix constituents, chondroitin sulfate proteoglycan (CSPG) or type II collagen. The molecular weights of guanidine-extracted proteoglycan (PG) and of protease-released chondroitin sulfate (CS) were not different from those of controls. Chondroitinase digestion of [3H]glucosamine-labeled CS yielded normal ratios of sulfated:nonsulfated disaccharides. Upon addition of hyaluronate to the PG extract there was normal interaction between these two macromolecules. Collagen was determined to be type II and contained normal amounts of glycosyl and hydroxyl residues. Incorporation rates of labeled precursors of both CSPG and collagen were normal suggesting that the abnormality does not involve differences in rate of synthesis of these macromolecules. These data provide evidence that the genes involved with the synthesis and posttranslational modification of proteoglycan and collagen are not affected by a mutation at the cho locus.