A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis

AbstractMice 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 wider at the metaphyses than normal bones and only about half the normal length. By linkage analysis, the cho gene and the gene encoding the α1 (XI) chain of cartilage collagen XI were mapped to the same region of chromosome 3. Deletion of a cytidine residue about 570 nt downstream of the translation initiation codon in cho α1(XI) mRNA causes a reading frame shift and introduces a premature stop codon. The data demonstrate that collagen XI is essential for normal formation of cartilage collagen fibrils and the cohesive properties of cartilage. The results also suggest that the normal differentiation and spatial organization of growth plate chondrocytes is critially dependent on the presence of type XI collagen in cartilage extracellular matrix