Inactivation of the Gdf6 gene in this knockout strain causes defects in joint, ligament, and cartilage formation in sites including the wrist, ankle, the middle ear, and the coronal suture between bones in the skull.
David Kingsley, Stanford University School of Medicine
Gdf6 (growth differentiation factor 6) belongs to a distinct subgroup of the bone morphogenetic protein (BMP) family of secreted signaling molecules.
Animals homozygous for this knockout allele, incorporating an exon 2 deletion in the mouse Gdf6 gene, exhibit fusions between specific bones in the wrists and ankles. Fusions between 2 or 3 carpal bones are seen in most mutant mice. Some mutant mice also show a general disorganization of carpal bones. Fusions are also seen between tarsal bones in the ankle and the talus is consistently fused to the central tarsal bone. Some bones including the first distal tarsal element in the ankle and the middle ear bones (the malleus, incus and stapes) have altered shapes and are reduced in size. The annular ligament, surrounding the stapes is also reduced in size. In addition, the coronal suture between the frontal and parietal bones in the skull is consistently missing (craniosynostosis). Occasional carpal and tarsal fusions are seen in heterozygous mice. Heterozygotes are viable and fertile. Homozygous animals are recoverable, but at numbers lower than those predicted by Mendelian ratios. The ratio of homozygotes at E18.5 is normal, suggesting increased mortality in the perinatal period. Those homozygotes that survive exhibit subfertility and are small.
Exon 2, encoding the entire mature signaling region and 120 amino acids of the pro region, was replaced with a neomycin resistance selection cassette. The mutation was created through homologous recombination in (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. Chimeric animals were crossed with C57BL/6 mice. This strain was backcrossed to C57BL/6 for an unknown number of generations by the donating laboratory.
|Allele Name||targeted mutation 1, David M Kingsley|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Gdf6, growth differentiation factor 6|
|Site of Expression||Inactivation of the Gdf6 gene causes defects in joint, ligament, and cartilage formation.|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A genomic fragment containing exon 2 was replaced with a neomycin selection cassette inserted by homologous recombination. The deleted region encoded the entire mature signalling region and 120 amino acids of the pro region.|
Heterozygotes are viable and fertile. Homozygous animals show some perinatal lethality. Those that survive exhibit subfertility and are small.
When using the B6;129-Gdf6tm1Kng/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024648 in your Materials and Methods section.