Early neonatal death in mice homozygous for a null allele of the insulin receptor gene

摘要: Insulin action is viewed as a set of branching pathways, with some actions serving to regulate energy metabolism and others cellular growth development1. Thus far, available genetic evidence has supported this view. In humans, complete lack insulin receptors due mutations the receptor gene results in severe retardation mild diabetes2,3. mice, targeted inactivation sub-strate-1, an important substrate kinase, leads inhibition resistance metabolic insulin4,5. To address question whether both growth-promoting are mediated by receptor, we have generated mice lacking mutagenesis embryo-derived stem (ES) cells. Unlike human patients receptors6–9, homozygous for null allele born at term apparently normal intrauterine development. Within hours birth, however, develop hyperglycaemia hyperketonaemia, die result diabetic ketoacidosis 48–72 hours. These data consistent model which functions primarily mediate insulin.