Genetically engineered mice for studies of stress-related clinical conditions

Genetically engineered mice with a specific deletion of targeted genes provide a novel and useful tool to study the endogenous mechanisms underlying aberrant behaviour. In this review we take the stress hormone (hypothalamic-pituitary-adrenocortical) system as an example to demonstrate how refined molecular technologies have allowed to target individual genes involved in stress hormone regulation. We describe different gene targeting methods: the generation of "conventional" knock-out mice enables us to delete a gene of interest in every cell of the body. Equally important for the studies of gene function in the mouse is the use of tissue-specific regulatory systems that allow gene inactivation to be restricted to specific tissues and, in some cases, to specific time points during development, such as the "conditional" knock-out, or the application of antisense techniques. Importantly, deletion of individual genes is not providing animal models for certain psychiatric disorders as these are caused by a manifold of minor changes in a series of so-called susceptibility genes. However, these gene targeting methods have become valuable tools to dissect the functions of individual components of complex biological systems in behavioural neuroscience: genetically engineered animals help to unravel the complex interactions and correlations between individual genes, hormonal regulation and behaviour, the most complex form of biological organization. (C) 2002 Elsevier Science Ltd. All rights reserved.