Mice lacking matrilin-1 (cartilage matrix protein) have alterations in type II collagen fibrillogenesis and fibril organization

Matrilin-1 (cartilage matrix protein) is a homotrimeric protein that forms collagen-dependent and collagen-independent fibrils in the extracelluar mat rix of cartilage. In the growth plate of developing long bones, the gene fo r matrilin-1 is transcribed exclusively by the chondrocytes of the zone of maturation which is situated between the zones of proliferation and hypertr ophy. When associated with the cartilage collagen fibril, which consists of collagens type II, IX, and SI, matrilin-1 displays a periodicity of 59.3 n m. Matrilin-1 also interacts with the proteoglycan, aggrecan. Because of it s association with the collagen fibril, we tested the hypothesis that matri lin-1 may play a role in collagen fibril formation and cartilage matrix ass embly by generating mice with targeted mutations in the matrilin-1 gene. Ul trastructural studies of the cartilage of growth plates of matrilin-1 null mice reveal an abnormal type II collagen fibrillogenesis and fibril organiz ation in the matrix of the zone of maturation. These results represent the first report on the regulation of the heterotypic type II collagen fibril b y a non-collagenous protein. The abnormal fibrillogenesis had no obvious ef fects on skeletal development, on the organization of chondrocytes in the g rowth plate and on the deposition of aggrecan and the hypertrophic-specific type X collagen in the cartilaginous matrix. (C) 1999 Wiley-Liss, Inc.