Abnormalities in aggression and anxiety in transgenic mice overexpressing activin E

To study the function of activin E, a TGF-beta superfamily member, in the regulation of affective behavior, we investigated the behavior of transgenic mice overexpressing activin E (TgActbetaE mice). Male TgActbetaE mice showed aggressive behavior in resident-intruder tests. In elevated plus-maze tests, the percentage of open arm entries was significantly increased in female TgActbetaE mice compared with that in wild-type mice. Furthermore, female TgActbetaE mice stayed in the central area for a significantly longer time than wild-type mice in open field tests. These results indicated that TgActbetaE mice had less anxiety-like behavior. The number of restraint-stress-evoked c-Fos-positive cells in the hypothalamic paraventricular nucleus in TgActbetaE mice was significantly decreased compared with that in wild-type mice. This suggests that synthesis of corticotrophin-releasing hormone induced by stress was decreased in TgActbetaE mice. Taking these results together, activin E may act as a regulator of the hypothalamic-pituitary-adrenal axis.