Finally, we investigated whether the alterations observed in Alx3-deficient embryos from diabetic pregnancies correlated with altered expression of genes controlling embryonic programs for mesenchyme development. We chose representative examples of genes whose deficiencies have been documented to be associated with developmental defects with partial penetrance. We found that in diabetic pregnancies, expression of Ap2 49, Bmp4 50 and Pdgfrα 51 was reduced in Alx3-deficient embryos as compared with wild type embryos (Fig. 6). In contrast, we did not find significant changes in the expression of Gcn5, which encodes a histone acetyltransferase not involved in mesenchyme development52, 53. No differences in the expression of these genes were found between wild type and Alx3-null embryos from non-diabetic pregnancies. Thus, these results show that impaired expression of some developmental genes only appears when both Alx3-deficiency and diabetes are present.Figure 6Altered gene expression in Alx3-deficient embryos from diabetic pregnancies. Relative levels of mRNA encoding representative developmentally regulated genes in wild type (white bars) or Alx3-null (black bars) embryos obtained from non-diabetic (ND) or diabetic (D) mothers. Values represent mean \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathop{+}\limits_{-}$$\end{document}+− s.e.m. *p < 0.05, Student’s t-test (n = 7 per group).