Dexamethasone nonsuppression in transgenic mice expressing antisense RNA to the glucocorticoid receptor.

Transgenic mice with impaired glucocorticoid receptor (GR) function produced by partially knocking out GR gene expression with antisense RNA were treated with increasing dosages of dexamethasone. In these mice, ten-fold higher dexamethasone dosages were required to induce full suppression of plasma corticosterone than in normal mice. This relative dexamethasone insensitivity adds to the evidence that these transgenic mice could serve as an appropriate model to study the negative feedback disturbance of the hypothalamic-pituitary-adrenocortical system in affective disorders.