The incidence of malformations was analysed by the Fisher exact test. The presence of synergism between hyperglycaemia and Alx3 deficiency was tested by comparing observed and expected malformation frequencies using χ2 test. All other data are expressed as mean ± s.e.m., and were analysed by Student’s t-test or two-way ANOVA followed by Bonferroni transformation, using Package GraphPad Prism 6 software.