Mammalian Genome

, Volume 11, Issue 12, pp 1087–1092 | Cite as

Abnormal growth plate function in pigs carrying a dominant mutation in type X collagen

  • Vivi H.  Nielsen
  • Christian  Bendixen
  • Jens  Arnbjerg
  • Charlotte M.  Sørensen
  • Henrik E.  Jensen
  • Naseer M.  Shukri
  • B.  Thomsen

Abstract.

We have identified a naturally occurring, dominant mutation that causes dwarfism in domestic pigs (Sus scrofa). With a positional candidate gene approach, the dwarf phenotype was shown to be a result of a single amino acid change, G590R, in the α1(X) chain of type X collagen. Type X collagen is a homotrimer of α1(X) chains encoded by the COL10A1 gene, which is expressed in hypertrophic chondrocytes during the process of endochondral ossification. An amino acid substitution at the equivalent position in human type X collagen, G595E, has previously been shown to cause Schmid metaphyseal chondrodysplasia (SMCD), which is a relatively mild skeletal disorder associated with dwarfism and growth plate abnormality. Consistent with the clinical phenotype of SMCD patients, radiological and histological examination of the dwarf pigs revealed metaphyseal chondrodysplasia in the long bones. Yeast-based, two-hybrid protein interaction studies and in vitro assembly experiments demonstrated that the amino acid substitution interfered with the ability of the mutated collagen molecules to engage in trimerization. This work establishes that the chondrodysplastic dwarf pigs by genetic, biochemical, radiological and histological criteria provide a valid animal model of SMCD.

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Copyright information

© Springer-Verlag New York Inc. 2000

Authors and Affiliations

  • Vivi H.  Nielsen
    • 1
  • Christian  Bendixen
    • 1
  • Jens  Arnbjerg
    • 2
  • Charlotte M.  Sørensen
    • 3
  • Henrik E.  Jensen
    • 3
  • Naseer M.  Shukri
    • 1
  • B.  Thomsen
    • 1
  1. 1.Department of Animal Breeding and Genetics, Danish Institute of Agricultural Sciences, PO Box 50, DK-8830 Tjele, DenmarkDK
  2. 2.Department of Clinical Studies, The Royal Veterinary and Agricultural University, DK-1870 Frederiksberg C, DenmarkDK
  3. 3.Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, DK-1870 Frederiksberg C, DenmarkDK

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