ABSENCE OF THE ALPHA-1(IX)-CHAIN LEADS TO A FUNCTIONAL KNOCK-OUT OF THE ENTIRE COLLAGEN-IX PROTEIN IN MICE

Cartilage fibrils contain collagen II as well as smaller amounts of co llagens IX and XI, The three collagens are thought to co-assemble into cartilage-specific arrays, The precise role of collagen IX in cartila ge has been addressed previously by generating mice harboring an inact ivated Col9a1 gene encoding the alpha 1(IX) chain, i.e. one of the thr ee constituent chains of collagen IX (Fassler, R., Schnegelsberg, P. N . J., Dausman, J., Shinya, T,, Muragaki, Y,, McCarthy, M, T,, Olsen, B , R,, and Jaenisch, R, (1994) Proc. Natl, Acad. Sci, U, S, A. 91, 5070 -5074), The animals did not produce alpha 1(M) mRNA or polypeptides an d were born with no conspicuous skeletal abnormality but post-natally developed early onset osteoarthritis, Here we show that the deficiency in alpha 1(M) chains leads to a functional knock-out of all polypepti des of collagen IX, whereas the Col9a2 and Col9a3 genes were normally transcribed, Therefore, synthesis of alpha 1(M) polypeptides is essent ial for the assembly of heterotrimeric collagen IX molecules, Surprisi ngly, cartilage fibrils of all shapes and banding patterns found in no rmal newborn, adolescent, or adult mice were formed in transgenic anim als, although they lacked collagen IX. Therefore, collagen IX is not e ssen tial, and may be functionally redundant, in fibrillogenesis in ca rtilage in vivo, The protein is required, however, for long term tissu e stability, presumably by mediating interactions between fibrillar an d extrafibrillar macromolecules.