Absence of the α1(IX) Chain Leads to a Functional Knock-out of the Entire Collagen IX Protein in Mice

• Published in: The Journal of biological chemistry 1997-08, Vol.272 (33), p.20650
• Main Authors: Rupert Hagg, Erik Hedbom, Uta Möllers, Attila Aszódi, Reinhard Fässler, Peter Bruckner
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.33.20650

Cartilage fibrils contain collagen II as well as smaller amounts of collagens IX and XI. The three collagens are thought to co-assemble into cartilage-specific arrays. The precise role of collagen IX in cartilage has been addressed previously by generating mice harboring an inactivated Col9a1 gene encoding the α1(IX) chain, i.e. one of the three constituent chains of collagen IX (Fässler, 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 α1(IX) mRNA or polypeptides and were born with no conspicuous skeletal abnormality but post-natally developed early onset osteoarthritis. Here we show that the deficiency in α1(IX) chains leads to a functional knock-out of all polypeptides of collagen IX, whereas the Col9a2 and Col9a3 genes were normally transcribed. Therefore, synthesis of α1(IX) polypeptides is essential for the assembly of heterotrimeric collagen IX molecules. Surprisingly, cartilage fibrils of all shapes and banding patterns found in normal newborn, adolescent, or adult mice were formed in transgenic animals, although they lacked collagen IX. Therefore, collagen IX is not essential, and may be functionally redundant, in fibrillogenesis in cartilage in vivo . The protein is required, however, for long term tissue stability, presumably by mediating interactions between fibrillar and extrafibrillar macromolecules.