Stimulation of the expression of genes encoding oxidative stress-scavenging enzymes has been proposed to act as a mechanism of defence against damage induced by ROS during diabetic pregnancy26, 27. Our data indicate that Alx3 is important for this mechanism of defence for three reasons. First, elevations in glucose concentrations stimulate the expression of Alx3, which therefore serves as a glucose sensor to initiate a transcriptional program of defence. Second, glucose-induced stimulation of Alx3 expression is required for the stimulation of oxidative stress-scavenging genes. And third, Alx3 is required for the glucose-induced expression of Foxo1, a well-known stimulator of oxidative stress-scavenging gene expression during the antioxidant defence response16, 47, 48, 56, 57.