Increased Cdx protein dose effects upon axial patterning in transgenic lines of mice

To investigate the link between Cdx protein concentration and axial patterning in embryos, we made lines of mice OE1, OE2 and OE4 that overexpress each of the Cdx genes Cdx1, Cdx2 and Cdx4, respectively. The lines carry Cdx transgenes under the transcriptional control of their own promoter/enhancer elements. Transgenic embryos show Cdx transcription at 8.5 to 8.7 days within normal spatial domains for Cdx expression (primitive streak/tailbud), yet, overall, they contain elevated levels of Cdx proteins. Increased doses of Cdx proteins result in homeotic shifts in vertebral types along most of the vertebral column, with transformations being most obvious within the cervical region. Most of the shifts are anterior-to-posterior transformations and the anterior limits of these are commonly skull/vertebra 1 (v1) for OE1, v1/v2 for OE2 and v7 for OE4. OE embryos display anterior shifts in the expression of a Hoxa7/lacZ reporter within neural, paraxial and lateral plate mesoderm tissues. Hoxa7/lacZ expression commences at the normal time in OE1 and OE4 embryos. OE2 embryos display a forward shift in the gradient of Cdx2 protein along the axis, suggesting that a Cdx morphogen gradient model could account, at least in part, for the homeotic shifts in vertebral types. OE mice display additional defects: forelimb deficiencies in OE1, multiple tail axes, vertebral mis-alignments and axial truncations in OE2.