mice lacking alpha 1 ix collagen develop noninflammatory degenerative joint disease type ix collagen is a nonfibrillar collagen composed of three gene products alpha 1ix alpha 2ix and alpha 3ix type ix molecules are localized on the surface of type iicontaining fibrils and consist of two arms a long arm that is crosslinked to type ii collagen and a short arm that projects into the perifibrillar space in hyaline cartilage the alpha 1ix collagen transcript encodes a polypeptide with a large nterminal globular domain nc4 whereas in many other tissues an alternative transcript encodes an alpha 1ix chain with a truncated nc4 domain it has been proposed that type ix molecules are involved in the interaction of fibrils with each other or with other components of the extracellular matrix to test this hypothesis we have generated a mouse strain lacking both isoforms of the alpha 1ix chain homozygous mutant mice are viable and show no detectable abnormalities at birth but develop a severe degenerative joint disease resembling human osteoarthritis