Developmental failure of the intra-articular ligaments in mice with absence of growth differentiation factor 5

Osteoarthritis Cartilage. 2007 Apr;15(4):468-74. doi: 10.1016/j.joca.2006.09.003. Epub 2006 Oct 17.


Objective: To show the phenotypic characteristics of the knee joints in brachypodism mice (bp mice), which carry a functional null mutation of the growth differentiation factor 5 (GDF5) gene, we investigated the adult and embryonic bp mice.

Method: Radiographic and macroscopic examinations of the knee joint of adult bp mice were performed. A histological examination of the knee joint of bp mice from E12.5 to E18.5 was also performed.

Results: Radiographic and macroscopic examinations of the adult bp mice showed anterior dislocation, hypoplastic condyles, and absence of the intra-articular ligaments. Safranin O staining of knee joints of the embryonic bp mice showed severe hypoplasty of the chondroepiphyses and intra-articular ligaments at E16.5. There was no difference in the number and location of 5-bromo-2'-deoxyuridine (BrdU)-positive cells between wild-type and bp mice through E12.5 to E14.5. A terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) study showed excessive cell death of mesenchymal cells of the future knee joint in bp mice at E12.5 and E13.5.

Conclusion: bp mice exhibit developmental failure of the condyles and intra-articular ligament of the knee joints.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Bone Morphogenetic Proteins / deficiency*
  • Bone Morphogenetic Proteins / genetics
  • Growth Differentiation Factor 5
  • Knee Joint / growth & development*
  • Ligaments, Articular / growth & development*
  • Limb Deformities, Congenital / genetics*
  • Mice


  • Bone Morphogenetic Proteins
  • Gdf5 protein, mouse
  • Growth Differentiation Factor 5