Endochondral ossification is the prevalent mode of vertebrate skeleton
formation; it starts during embryogenesis when cartilage models of lo
ng bones develop central regions of hypertrophy which are replaced by
bony trabeculae and bone marrow. Although several transcription factor
s have been implicated in pattern formation in the limbs and axial ske
leton, little is known about the transcriptional regulations involved
in bone formation. We have created a null allele in the mouse Krox-20
gene, which encodes a zinc finger transcription factor, by in frame in
sertion of the E. coli lacZ gene and shown that hindbrain segmentation
and peripheral nerve myelination are affected in Krox-20(-/-) embryos
. We report here that Krox-20 is also activated in a subpopulation of
growth plate hypertrophic chondrocytes and in differentiating osteobla
sts and that its disruption severely affects endochondral ossification
. Krox-20(-/-) mice develop skeletal abnormalities including a reduced
length and thickness of newly formed bones, a drastic reduction of ca
lcified trabeculae and severe porosity. The periosteal component to bo
ne formation and calcification does not appear to be affected in the h
omozygous mutant suggesting that the major role for Krox-20 is to be f
ound in the control of the hypertrophic chondrocyte-osteoblast interac
tions leading to endosteal bone formation.