Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10

PLoS One. 2013 Sep 25;8(9):e75621. doi: 10.1371/journal.pone.0075621. eCollection 2013.


The skeletal dysplasias are disorders of the bone and cartilage tissues. Similarly to humans, several dog breeds have been reported to suffer from different types of genetic skeletal disorders. We have studied the molecular genetic background of an autosomal recessive chondrodysplasia that affects the Norwegian Elkhound and Karelian Bear Dog breeds. The affected dogs suffer from disproportionate short stature dwarfism of varying severity. Through a genome-wide approach, we mapped the chondrodysplasia locus to a 2-Mb region on canine chromosome 17 in nine affected and nine healthy Elkhounds (praw = 7.42×10(-6), pgenome-wide = 0.013). The associated locus contained a promising candidate gene, cartilage specific integrin alpha 10 (ITGA10), and mutation screening of its 30 exons revealed a nonsense mutation in exon 16 (c.2083C>T; p.Arg695*) that segregated fully with the disease in both breeds (p = 2.5×10(-23)). A 24% mutation carrier frequency was indicated in NEs and an 8% frequency in KBDs. The ITGA10 gene product, integrin receptor α10-subunit combines into a collagen-binding α10β1 integrin receptor, which is expressed in cartilage chondrocytes and mediates chondrocyte-matrix interactions during endochondral ossification. As a consequence of the nonsense mutation, the α10-protein was not detected in the affected cartilage tissue. The canine phenotype highlights the importance of the α10β1 integrin in bone growth, and the large animal model could be utilized to further delineate its specific functions. Finally, this study revealed a candidate gene for human chondrodysplasias and enabled the development of a genetic test for breeding purposes to eradicate the disease from the two dog breeds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Diseases, Developmental / etiology*
  • Bone Diseases, Developmental / genetics*
  • Bone Diseases, Developmental / pathology
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Cartilage / metabolism*
  • Chondrocytes / metabolism
  • Chromosomes, Mammalian / genetics
  • Codon, Nonsense / genetics*
  • Collagen / genetics
  • Dogs
  • Exons / genetics
  • Genetic Testing / methods
  • Humans
  • Integrin alpha Chains / genetics*
  • Pedigree
  • Protein Binding / genetics


  • Codon, Nonsense
  • Integrin alpha Chains
  • integrin alpha 10
  • Collagen

Grants and funding

This study was supported partly by the Academy of Finland, the Sigrid Juselius Foundation, Biocentrum Helsinki, the Jane and Aatos Erkko Foundation and the University of Helsinki Research Funds. HL is a member of Biocentrum Helsinki and KK is a student in the Helsinki Graduate Program in Biotechnology and Molecular Biology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.