A loss of aggressive behaviour and its reinstatement by oestrogen in mice lacking the aromatase gene (Cyp19)

Aromatase P450 (CYP19) is an enzyme responsible for conversion of androgens to oestrogens. We generated CYP19 knockout (ArKO) mice by targeting disrup tion of the CYP19, gene and observed that the ArKO males exhibited a comple te loss of aggressive behaviour against intruder mice when examined using a resident-intruder paradigm. The defect: in the behaviour of ArKO males was reinstated when the mice received supplements of 17 beta -estradiol soon a fter birth. Nevertheless, the cumulative duration of the behaviour displaye d by the treated mice during the test period of 15 min was 19 +/- 10 s, whi ch was much shorter than that displayed by wild-type males, 90 +/- 17 s. Wh en the supplementation was started at 7 days after birth, the defect was no t restored. These findings illustrate an absolute requirement for oestrogen during the neonatal stage of a male's life for the development of the pote ntial for aggression observed in adulthood. Furthermore, the present study demonstrates that ArKO males are a useful model in which to investigate the neural mechanisms by which aggressive behaviour is controlled.