Mice with mutations in the HPA-system as models for symptoms of depression

Genetically engineered mice hold promise to help us understand the effects of enhanced or reduced gene activity upon behavior and metabolism. Because many basic and clinical studies suggest that alterations of the hypothalamic pituitary adrenocortical (HPA) system are involved in the development and course of depression, mouse mutants with genetic modifications of genes regulating the HPA system were generated. This review summarizes these effects and concludes that advanced technologies allowing for regional overexpression or inactivation of genes or introduction of polymorphisms into the mouse genome are well suited to explain individual symptoms or symptom patterns prevalent among depressives. However, as depression is a complex disorder in which minor changes of many genes as well as environmental factors (including epigenetic programming) play a causal role and determine the phenotype, the use of mice with single gene mutations needs to be critically discussed when attempting to create a genetic animal model of depression.