Abnormal stress response and increased fighting behavior in mice lacking the bcr gene product

The in vivo function of proteins which regulate activity of the GTPase Rac is largely unknown. Here we establish that mice lacking bcr, a known GTPase activating protein for Rac, exhibit a defect in the regulation of both hormonal and behavioral stress responses. Bcr null mutants demonstrate prolonged elevation of plasma glucocorticoids and increased fighting in males in response to physiological and social stress, respectively. Combined biochemical and behavioral data indicate that bcr is involved in mediating the cellular effects of glucocorticoids, specifically down-regulation of the stress-activated hippocampal hypothalamic-pituitary-adrenal axis.