Since Alx3-deficient mice do not develop overt diabetes upon pregnancy, we induced diabetic gestations by treating female mice with streptozotocin to provoke the selective destruction of pancreatic islets, a widely accepted and commonly used method for the study of diabetic embryopathy5–10, 13, 16, 20, 23, 40–43. Pancreatic islet destruction by streptozotocin was reflected by the appearance of hyperglycaemia, which was corrected by subcutaneous implantation of insulin pellets (Fig. 1C). Prior to mating, all streptozotocin-treated female mice implanted with insulin pellets were checked to have similar fasting glucose levels within normal values, indicating the effectiveness of insulin released from the pellets (Fig. 1C). After mating, blood glucose levels increased progressively as a consequence of pregnancy. One week after the onset of gestation they reached values higher than 250 mg/dl, and continued to increase until embryos were extracted for analyses after 10.5 days of gestation (Fig. 1C). This severe hyperglycaemia was not due to exhaustion of the insulin content of the pellets, because streptozotocin-treated non-pregnant females did not develop hyperglycaemia after insulin pellet implantation during a similar period of time.