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Proc Natl Acad Sci U S A. May 24, 1994; 91(11): 5070–5074.

Mice lacking alpha 1 (IX) collagen develop noninflammatory degenerative joint disease.


Type IX collagen is a nonfibrillar collagen composed of three gene products, alpha 1(IX), alpha 2(IX), and alpha 3(IX). Type IX molecules are localized on the surface of type II-containing 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 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 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 1(IX) chain. Homozygous mutant mice are viable and show no detectable abnormalities at birth but develop a severe degenerative joint disease resembling human osteoarthritis.

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  • Shaw LM, Olsen BR. FACIT collagens: diverse molecular bridges in extracellular matrices. Trends Biochem Sci. 1991 May;16(5):191–194. [PubMed]
  • Vaughan L, Mendler M, Huber S, Bruckner P, Winterhalter KH, Irwin MI, Mayne R. D-periodic distribution of collagen type IX along cartilage fibrils. J Cell Biol. 1988 Mar;106(3):991–997. [PMC free article] [PubMed]
  • van der Rest M, Mayne R. Type IX collagen proteoglycan from cartilage is covalently cross-linked to type II collagen. J Biol Chem. 1988 Feb 5;263(4):1615–1618. [PubMed]
  • Wu JJ, Woods PE, Eyre DR. Identification of cross-linking sites in bovine cartilage type IX collagen reveals an antiparallel type II-type IX molecular relationship and type IX to type IX bonding. J Biol Chem. 1992 Nov 15;267(32):23007–23014. [PubMed]
  • Vasios G, Nishimura I, Konomi H, van der Rest M, Ninomiya Y, Olsen BR. Cartilage type IX collagen-proteoglycan contains a large amino-terminal globular domain encoded by multiple exons. J Biol Chem. 1988 Feb 15;263(5):2324–2329. [PubMed]
  • Yada T, Suzuki S, Kobayashi K, Kobayashi M, Hoshino T, Horie K, Kimata K. Occurrence in chick embryo vitreous humor of a type IX collagen proteoglycan with an extraordinarily large chondroitin sulfate chain and short alpha 1 polypeptide. J Biol Chem. 1990 Apr 25;265(12):6992–6999. [PubMed]
  • Wright DW, Mayne R. Vitreous humor of chicken contains two fibrillar systems: an analysis of their structure. J Ultrastruct Mol Struct Res. 1988 Sep;100(3):224–234. [PubMed]
  • Svoboda KK, Nishimura I, Sugrue SP, Ninomiya Y, Olsen BR. Embryonic chicken cornea and cartilage synthesize type IX collagen molecules with different amino-terminal domains. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7496–7500. [PMC free article] [PubMed]
  • Fitch JM, Mentzer A, Mayne R, Linsenmayer TF. Acquisition of type IX collagen by the developing avian primary corneal stroma and vitreous. Dev Biol. 1988 Aug;128(2):396–405. [PubMed]
  • Swiderski RE, Solursh M. Localization of type II collagen, long form alpha 1(IX) collagen, and short form alpha 1(IX) collagen transcripts in the developing chick notochord and axial skeleton. Dev Dyn. 1992 Jun;194(2):118–127. [PubMed]
  • Perris R, Krotoski D, Bronner-Fraser M. Collagens in avian neural crest development: distribution in vivo and migration-promoting ability in vitro. Development. 1991 Nov;113(3):969–984. [PubMed]
  • Hayashi M, Hayashi K, Iyama K, Trelstad RL, Linsenmayer TF, Mayne R. Notochord of chick embryos secretes short-form type IX collagen prior to the onset of vertebral chondrogenesis. Dev Dyn. 1992 Jul;194(3):169–176. [PubMed]
  • Nishimura I, Muragaki Y, Olsen BR. Tissue-specific forms of type IX collagen-proteoglycan arise from the use of two widely separated promoters. J Biol Chem. 1989 Nov 25;264(33):20033–20041. [PubMed]
  • Muragaki Y, Nishimura I, Henney A, Ninomiya Y, Olsen BR. The alpha 1 (IX) collagen gene gives rise to two different transcripts in both mouse embryonic and human fetal RNA. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2400–2404. [PMC free article] [PubMed]
  • McBurney MW, Sutherland LC, Adra CN, Leclair B, Rudnicki MA, Jardine K. The mouse Pgk-1 gene promoter contains an upstream activator sequence. Nucleic Acids Res. 1991 Oct 25;19(20):5755–5761. [PMC free article] [PubMed]
  • Rudnicki MA, Braun T, Hinuma S, Jaenisch R. Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell. 1992 Oct 30;71(3):383–390. [PubMed]
  • Doetschman TC, Eistetter H, Katz M, Schmidt W, Kemler R. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol. 1985 Jun;87:27–45. [PubMed]
  • Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992 Jun 12;69(6):915–926. [PubMed]
  • Auffray C, Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. [PubMed]
  • Feinberg AP, Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. [PubMed]
  • Oh SP, Griffith CM, Hay ED, Olsen BR. Tissue-specific expression of type XII collagen during mouse embryonic development. Dev Dyn. 1993 Jan;196(1):37–46. [PubMed]
  • Warman M, Kimura T, Muragaki Y, Castagnola P, Tamei H, Iwata K, Olsen BR. Monoclonal antibodies against two epitopes in the human alpha 1 (IX) collagen chain. Matrix. 1993 Mar;13(2):149–156. [PubMed]
  • Saga Y, Yagi T, Ikawa Y, Sakakura T, Aizawa S. Mice develop normally without tenascin. Genes Dev. 1992 Oct;6(10):1821–1831. [PubMed]
  • Soriano P, Montgomery C, Geske R, Bradley A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991 Feb 22;64(4):693–702. [PubMed]
  • Lee KF, Li E, Huber LJ, Landis SC, Sharpe AH, Chao MV, Jaenisch R. Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell. 1992 May 29;69(5):737–749. [PubMed]
  • Hamerman D. The biology of osteoarthritis. N Engl J Med. 1989 May 18;320(20):1322–1330. [PubMed]
  • Brierley VH, Ayad S, Grant ME. Types II, VI and IX collagens in normal and osteoarthrotic human articular cartilage. Biochem Soc Trans. 1991 Nov;19(4):379S–379S. [PubMed]
  • Okada Y, Shinmei M, Tanaka O, Naka K, Kimura A, Nakanishi I, Bayliss MT, Iwata K, Nagase H. Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium. Lab Invest. 1992 Jun;66(6):680–690. [PubMed]
  • Morgan K, Clague RB, Collins I, Ayad S, Phinn SD, Holt PJ. Incidence of antibodies to native and denatured cartilage collagens (types II, IX, and XI) and to type I collagen in rheumatoid arthritis. Ann Rheum Dis. 1987 Dec;46(12):902–907. [PMC free article] [PubMed]
  • Boissier MC, Chiocchia G, Ronziere MC, Herbage D, Fournier C. Arthritogenicity of minor cartilage collagens (types IX and XI) in mice. Arthritis Rheum. 1990 Jan;33(1):1–8. [PubMed]
  • Nakata K, Ono K, Miyazaki J, Olsen BR, Muragaki Y, Adachi E, Yamamura K, Kimura T. Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alpha 1(IX) collagen chains with a central deletion. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2870–2874. [PMC free article] [PubMed]

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