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Spondylometaphyseal dysplasia in mice carrying a dominant negative mutation in a matrix protein specific for cartilage-to-bone transition

Nature volume 365, pages 56–61 (1993)Cite this article

Abstract

THE vertebrate skeleton is formed primarily by endochondral ossification, starting during embryogenesis when cartilage anlagens develop central regions of hypertrophic cartilage which are replaced by bony trabeculae and bone marrow1,2. During this process chondrocytes express a unique matrix molecule, type X collagen3. We report here that mice carrying a mutated collagen X transgene develop skeletal deformities including compression of hypertrophic growth plate cartilage and a decrease in newly formed bone, as well as leukocyte deficiency in bone marrow, reduction in size of thymus and spleen, and lymphopenia. The defects indicate that collagen X is required for normal skeletal morphogenesis and suggest that mutations in COL10A1 are responsible for certain human chondrodysplasias, such as Spondylometaphyseal dysplasias and metaphyseal chondrodysplasias4.

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References

  1. Ham, A. W. Histology 5th edn 384–457 (Lippincott, Philadelphia, 1965).

    Google Scholar 

  2. Caplan, A. I. & Pechak, D. G. Bone Min. Res. 5, 117–183 (1987).

    Google Scholar 

  3. Jacenko, O., Olsen, B. R. & LuValle, P. Crit. Rev. Eukaryotic Gene Exp. 1, 327–353 (1991).

    CAS  Google Scholar 

  4. McKusick, V. A., Francomano, C. A. & Antonarakis, S. E. (eds) Mendelian Inheritance in Man. Catalogs of Autosomat Dominant, Autosomal Recessive, and X-linked Phenotypes For examples, see Vol. 1, entry numbers 156500, 156400, 184250, 184253, and Vol. 2, entry numbers 250250, 260400, 271660 (The Johns Hopkins University Press, Baltimore, London, 1992).

  5. Schmid, T. M., Popp, R. G. & Linsenmayer, T. F. Ann. N.Y. Acad. Sci. 580, 64–73 (1990).

    Article  ADS  CAS  Google Scholar 

  6. Gibson, G. J. & Flint, M. H. J. Cell Biol. 101, 277–284 (1985).

    Article  CAS  Google Scholar 

  7. Brass, A., Kadler, K., Thomas, J. T., Grant, M. E. & Boot-Handford, R. P. FEBS Lett. 303, 126–128 (1992).

    Article  CAS  Google Scholar 

  8. Apte, S. S., Seldin, M. F., Hayashi, M. & Olsen, B. R. Eur. J. Biochem. 206, 217–224 (1992).

    Article  CAS  Google Scholar 

  9. LuValle, P., Ninomiya, Y., Rosenblum, N. D. & Olsen, B. R. J. biol. Chem. 263, 18378–18385 (1988).

    CAS  PubMed  Google Scholar 

  10. LuValle, P., Iwamoto, M., Fanning, P., Pacifici, M. & Olsen, B. R. J. Cell Biol. 121, 1173–1179.

  11. Grigoriadis, A., Heersche, J. M. & Aubin, J. E. Devl Biol. 142, 313–318 (1990).

    Article  CAS  Google Scholar 

  12. Summers, T. A., Irwin, M. H., Mayne, R. & Balian, G. J. biol. Chem. 263, 581–587 (1988).

    CAS  PubMed  Google Scholar 

  13. Iyama, K.-I. et al. Anat. Rec. 229, 462–472 (1991).

    Article  CAS  Google Scholar 

  14. Kwan, A. P. L., Cummings, C. E., Chapman, J. A. & Grant, M. E. J. Cell Biol. 114, 597–604 (1991).

    Article  CAS  Google Scholar 

  15. Sawada, H., Konomi, H. & Hirosawa, K. Eur. J. Cell Biol. 110, 219–227 (1990).

    Article  CAS  Google Scholar 

  16. Warman, M. L. et al. Nature Genet. (in the press).

  17. Ninomiya, Y. et al. in Extracellular Matrix Genes (eds Sandell, L. J. & Boyd, C. D.) 79–113 (Academic, New York, 1990).

    Book  Google Scholar 

  18. Luckow, B. & Schütz, G. Nucleic Acids Res. 15, 5490 (1987).

    Article  CAS  Google Scholar 

  19. Lair, P. W. et al. Nucleic Acids Res. 19, 4293 (1991).

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy and Cellular Biology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Olena Jacenko, Phyllis A. LuValle & Bjorn R. Olsen

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  1. Olena Jacenko
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  2. Phyllis A. LuValle
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  3. Bjorn R. Olsen
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Jacenko, O., LuValle, P. & Olsen, B. Spondylometaphyseal dysplasia in mice carrying a dominant negative mutation in a matrix protein specific for cartilage-to-bone transition. Nature 365, 56–61 (1993). https://doi.org/10.1038/365056a0

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