Survival of reproductive behaviors in estrogen receptor beta gene-deficient (betaERKO) male and female mice.

Previously, it was shown that the lack of a functional estrogen receptor (ER) alpha gene (ERalpha) greatly affects reproduction-related behaviors in both female and male mice. However, widespread expression of a novel second ER gene, ERbeta, demanded that we examine the possible participation of ERbeta in regulation of these behaviors. In dramatic contrast to our results with ERalpha knockout (alphaERKO) males, betaERKO males performed at least as well as wild-type controls in sexual behavior tests. Moreover, not only did betaERKO males exhibit normal male-typical aggressive behavior, including offensive attacks, but they also showed higher levels of aggression than wild-type mice under certain conditions of social experience. These data revealed a significant interaction between genotype and social experience with respect to aggressive behavior. Finally, females lacking a functional beta isoform of the ER gene showed normal lordosis and courtship behaviors, extending in some cases beyond the day of behavioral estrus. These results highlight the importance of ERalpha for the normal expression of natural reproductive behaviors in both sexes and also provide a background for future studies evaluating ERbeta gene contributions to other, nonreproductive behaviors.