MICE LACKING ALPHA(IX) COLLAGEN DEVELOP NONINFLAMMATORY DEGENERATIVE JOINT DISEASE

Type TX collagen is a nonfibrillar collagen composed of three gene pro ducts, alpha 1(IX), alpha 2(IX), and alpha 3(IX). Type IX molecules ar e localized on the surface of type II-containing fibrils and consist o f two arms, a long arm that is crosslinked to type II collagen and a s hort arm that projects into the perifibrillar space. In hyaline cartil age, the alpha 1(IX) collagen transcript encodes a polypeptide with a large N-terminal globular domain (NC4), whereas in many other tissues an alternative transcript encodes an alpha 1(IX) chain with a truncate d NC4 domain. It has been proposed that type IX molecules are involved in the interaction of fibrils with each other or with other component s of the extracellular matrix. To test this hypothesis, we have genera ted a mouse strain lacking both isoforms of the alpha 1(IX) chain. Hom ozygous mutant mice are viable and show no detectable abnormalities at birth but develop a severe degenerative joint disease resembling huma n osteoarthritis.