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Gene Review

Col2a1  -  collagen, type II, alpha 1

Mus musculus

Synonyms: Alpha-1 type II collagen, Col2, Col2a, Col2a-1, Collagen alpha-1(II) chain, ...
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Disease relevance of Col2a1


Psychiatry related information on Col2a1

  • Abnormal response to physical activity in femurs after heterozygous inactivation of one allele of the Col2a1 gene for type II collagen in mice [6].

High impact information on Col2a1

  • During chondrogenesis in the mouse, Sox9 is co-expressed with Col2a1, the gene encoding type-II collagen, the major cartilage matrix protein [7].
  • Homologous recombination in embryonic stem cells was used to prepare transgenic mice with an inactivated Col2a1 gene for collagen II, the major protein component of the extracellular matrix of cartilage [8].
  • The ECM protein Del-1 is one of several novel ECM proteins that accumulate around angiogenic blood vessels in embryonic and tumor tissue and promote angiogenesis in the absence of exogenous growth factors [9].
  • These changes may be responsible for the abnormal notochord removal in Col2a1-null mice [10].
  • Consistent with this finding, PGC-1alpha disruption in MSC by small interfering RNA inhibits Col2a1 expression during chondrogenesis [11].

Chemical compound and disease context of Col2a1


Biological context of Col2a1


Anatomical context of Col2a1


Associations of Col2a1 with chemical compounds

  • Additionally, we compare the impact of a glycine904 to cysteine (G904C) mutation in the triple helical coding domain of mouse Col2a1 with two previously reported Col2a1 mutations (exon7 deletion (Del1) and G85C) [2].
  • Treatment with DEX enhanced Col2a1 mRNA expression in these chondrocytes and furthermore, DEX enhanced the activity of Col2-CAT (chloramphenicol acetyltransferase) construct containing a 1.6 kb intron fragment where chondrocyte-specific Sry/Sox- consensus sequence is located [20].
  • RESULTS: Sequence analyses revealed that the affected gene is Col2a1, which has a missense mutation at exon 48 causing an amino acid change of arginine to cysteine at position 1417 [5].
  • The single base substitution in Col2a1 resulted in a glycine to serine mutation within the helical domain and corresponded to one previously identified in a patient with the lethal human chondrodysplasia, hypochondrogenesis (Horton et al. [1992] Proc. Natl. Acad. Sci. U.S.A. 89:4583-4587) [21].
  • Skeletal staining of complete litters with alcian blue/alizarin red S revealed that the onset of chondrogenesis and subsequent endochondral ossification were delayed in heterozygous and homozygous Del1 embryos [22].

Physical interactions of Col2a1


Co-localisations of Col2a1

  • Expression of Col2a1 colocalized with expression of Sox9 in all chondroprogenitor cells [16].

Regulatory relationships of Col2a1


Other interactions of Col2a1

  • The expression of Col2a1, a downstream response gene of Sox9, was also significantly increased upon BMP-2 addition [24].
  • The three proteins cooperatively activated the Col2a1- and aggrecan genes in cultured cells [17].
  • To directly examine the role of vascular endothelial growth factor (VEGFA) in cartilage development, we conditionally knocked out Vegfa in chondrocytes, using the Col2a1 promoter to drive expression of Cre recombinase [25].
  • Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1 tissue-specific enhancer [26].
  • When the Col2a1 promoter was replaced with a minimal beta-globin promoter, the 182 bp intron 1 sequence was still able to target expression of the transgene to chondrocytes [27].

Analytical, diagnostic and therapeutic context of Col2a1


  1. The role of collagen II and cartilage fibril-associated molecules in skeletal development. Aszódi, A., Hunziker, E.B., Olsen, B.R., Fässler, R. Osteoarthr. Cartil. (2001) [Pubmed]
  2. Impact of mutations of cartilage matrix genes on matrix structure, gene activity and chondrogenesis. So, C.L., Kaluarachchi, K., Tam, P.P., Cheah, K.S. Osteoarthr. Cartil. (2001) [Pubmed]
  3. A zinc finger transcription factor, alphaA-crystallin binding protein 1, is a negative regulator of the chondrocyte-specific enhancer of the alpha1(II) collagen gene. Tanaka, K., Matsumoto, Y., Nakatani, F., Iwamoto, Y., Yamada, Y. Mol. Cell. Biol. (2000) [Pubmed]
  4. Use of a new rat chondrosarcoma cell line to delineate a 119-base pair chondrocyte-specific enhancer element and to define active promoter segments in the mouse pro-alpha 1(II) collagen gene. Mukhopadhyay, K., Lefebvre, V., Zhou, G., Garofalo, S., Kimura, J.H., de Crombrugghe, B. J. Biol. Chem. (1995) [Pubmed]
  5. A missense mutation in the mouse Col2a1 gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis. Donahue, L.R., Chang, B., Mohan, S., Miyakoshi, N., Wergedal, J.E., Baylink, D.J., Hawes, N.L., Rosen, C.J., Ward-Bailey, P., Zheng, Q.Y., Bronson, R.T., Johnson, K.R., Davisson, M.T. J. Bone Miner. Res. (2003) [Pubmed]
  6. Abnormal response to physical activity in femurs after heterozygous inactivation of one allele of the Col2a1 gene for type II collagen in mice. Nieminen, J., Sahlman, J., Hirvonen, T., Jämsä, T., Tuukkanen, J., Kovanen, V., Kröger, H., Jurvelin, J., Arita, M., Li, S.W., Prockop, D.J., Hyttinen, M.M., Helminen, H.J., Lapveteläinen, T., Puustjärvi, K. Calcif. Tissue Int. (2005) [Pubmed]
  7. SOX9 directly regulates the type-II collagen gene. Bell, D.M., Leung, K.K., Wheatley, S.C., Ng, L.J., Zhou, S., Ling, K.W., Sham, M.H., Koopman, P., Tam, P.P., Cheah, K.S. Nat. Genet. (1997) [Pubmed]
  8. Transgenic mice with targeted inactivation of the Col2 alpha 1 gene for collagen II develop a skeleton with membranous and periosteal bone but no endochondral bone. Li, S.W., Prockop, D.J., Helminen, H., Fässler, R., Lapveteläinen, T., Kiraly, K., Peltarri, A., Arokoski, J., Lui, H., Arita, M. Genes Dev. (1995) [Pubmed]
  9. Neovascularization of ischemic tissues by gene delivery of the extracellular matrix protein Del-1. Zhong, J., Eliceiri, B., Stupack, D., Penta, K., Sakamoto, G., Quertermous, T., Coleman, M., Boudreau, N., Varner, J.A. J. Clin. Invest. (2003) [Pubmed]
  10. Collagen II is essential for the removal of the notochord and the formation of intervertebral discs. Aszódi, A., Chan, D., Hunziker, E., Bateman, J.F., Fässler, R. J. Cell Biol. (1998) [Pubmed]
  11. Transcriptional coactivator PGC-1alpha regulates chondrogenesis via association with Sox9. Kawakami, Y., Tsuda, M., Takahashi, S., Taniguchi, N., Esteban, C.R., Zemmyo, M., Furumatsu, T., Lotz, M., Belmonte, J.C., Asahara, H. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  12. Up regulation of cathepsin K expression in articular chondrocytes in a transgenic mouse model for osteoarthritis. Morko, J.P., Söderström, M., Säämänen, A.M., Salminen, H.J., Vuorio, E.I. Ann. Rheum. Dis. (2004) [Pubmed]
  13. The chondrogenic transcription factor Sox9 is a target of signaling by the parathyroid hormone-related peptide in the growth plate of endochondral bones. Huang, W., Chung, U.I., Kronenberg, H.M., de Crombrugghe , B. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  14. Mouse Snail family transcription repressors regulate chondrocyte, extracellular matrix, type II collagen, and aggrecan. Seki, K., Fujimori, T., Savagner, P., Hata, A., Aikawa, T., Ogata, N., Nabeshima, Y., Kaechoong, L. J. Biol. Chem. (2003) [Pubmed]
  15. Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation. Barbieri, O., Astigiano, S., Morini, M., Tavella, S., Schito, A., Corsi, A., Di Martino, D., Bianco, P., Cancedda, R., Garofalo, S. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  16. Parallel expression of Sox9 and Col2a1 in cells undergoing chondrogenesis. Zhao, Q., Eberspaecher, H., Lefebvre, V., De Crombrugghe, B. Dev. Dyn. (1997) [Pubmed]
  17. L-Sox5, Sox6 and Sox9 control essential steps of the chondrocyte differentiation pathway. Lefebvre, V., Behringer, R.R., de Crombrugghe, B. Osteoarthr. Cartil. (2001) [Pubmed]
  18. Type II and type IX collagen transcript isoforms are expressed during mouse testis development. McClive, P.J., Sinclair, A.H. Biol. Reprod. (2003) [Pubmed]
  19. Developmental expression analysis of murine autotaxin (ATX). Bächner, D., Ahrens, M., Betat, N., Schröder, D., Gross, G. Mech. Dev. (1999) [Pubmed]
  20. Dexamethasone enhances SOX9 expression in chondrocytes. Sekiya, I., Koopman, P., Tsuji, K., Mertin, S., Harley, V., Yamada, Y., Shinomiya, K., Nifuji, A., Noda, M. J. Endocrinol. (2001) [Pubmed]
  21. Skeletal development in transgenic mice expressing a mutation at Gly574Ser of type II collagen. Maddox, B.K., Garofalo, S., Smith, C., Keene, D.R., Horton, W.A. Dev. Dyn. (1997) [Pubmed]
  22. Retarded skeletal development in transgenic mice with a type II collagen mutation. Savontaus, M., Metsranta, M., Vuorio, E. Am. J. Pathol. (1996) [Pubmed]
  23. FGF signaling antagonizes cytokine-mediated repression of Sox9 in SW1353 chondrosarcoma cells. Schaefer, J.F., Millham, M.L., de Crombrugghe, B., Buckbinder, L. Osteoarthr. Cartil. (2003) [Pubmed]
  24. The transcription factor Sox9 is involved in BMP-2 signaling. Zehentner, B.K., Dony, C., Burtscher, H. J. Bone Miner. Res. (1999) [Pubmed]
  25. VEGFA is necessary for chondrocyte survival during bone development. Zelzer, E., Mamluk, R., Ferrara, N., Johnson, R.S., Schipani, E., Olsen, B.R. Development (2004) [Pubmed]
  26. Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1 tissue-specific enhancer. Bridgewater, L.C., Lefebvre, V., de Crombrugghe, B. J. Biol. Chem. (1998) [Pubmed]
  27. A 182 bp fragment of the mouse pro alpha 1(II) collagen gene is sufficient to direct chondrocyte expression in transgenic mice. Zhou, G., Garofalo, S., Mukhopadhyay, K., Lefebvre, V., Smith, C.N., Eberspaecher, H., de Crombrugghe, B. J. Cell. Sci. (1995) [Pubmed]
  28. Mint represses transactivation of the type II collagen gene enhancer through interaction with alpha A-crystallin-binding protein 1. Yang, X., Li, J., Qin, H., Yang, H., Li, J., Zhou, P., Liang, Y., Han, H. J. Biol. Chem. (2005) [Pubmed]
  29. Oligonucleotide decoy mimicking alphaA-crystallin-binding protein 1 binding site on mouse Col2a1 enhancer stimulates transcription from the adjacent Col2a1 promoter in chondrogenic ATDC5 cell. Yamagiwa, H., Yamada, Y., Bolander, M.E., Sarkar, G. Mol. Biotechnol. (2004) [Pubmed]
  30. Expression of Sox9 and type IIA procollagen during attempted repair of articular cartilage damage in a transgenic mouse model of osteoarthritis. Salminen, H., Vuorio, E., Säämänen, A.M. Arthritis Rheum. (2001) [Pubmed]
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