A FIBRILLAR COLLAGEN GENE, COL11A1, IS ESSENTIAL FOR SKELETAL MORPHOGENESIS

Mice that are homozygous for the autosomal recessive chondrodysplasia (cho) mutation die at birth with abnormalities in cartilage of limbs, ribs, mandible, and trachea. Limb bones of newborn cho/cho mice are wi der at the metaphyses than normal bones and only about half the normal length. By linkage analysis, the cho gene and the gene encoding the a lpha 1(XI) chain of cartilage collagen XI were mapped to the same regi on of chromosome 3. Deletion of a cytidine residue about 570 nt downst ream of the translation initiation codon in cho alpha 1(XI) mRNA cause s a reading frame shift and introduces a premature stop codon. The dat a demonstrate that collagen XI is essential for normal formation of ca rtilage collagen fibrils and the cohesive properties of cartilage. The results also suggest that the normal differentiation and spatial orga nization of growth plate chondrocytes is critially dependent on the pr esence of type XI collagen in cartilage extracellular matrix.