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


METHODS
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.


CONCLUSIONS
bp mice exhibit developmental failure of the condyles and intra-articular ligament of the knee joints.
Harada
M
M
Department of Orthopaedic Surgery, Yamagata University School of Medicine, Iida-Nishi-2-2-2, Yamagata 990-9585, Japan.
Takahara
M
M
Zhe
P
P
Otsuji
M
M
Iuchi
Y
Y
Takagi
M
M
Ogino
T
T
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000172:deficiency* / Q000235:genetics; D055428:Growth Differentiation Factor 5; D007719:Knee Joint / Q000254:growth & development*; D008023:Ligaments, Articular / Q000254:growth & development*; D017880:Limb Deformities, Congenital / Q000235:genetics*; D051379:Mice
D019485:Bone Morphogenetic Proteins; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5