Altered anxiety and defensive behaviors in Bax knockout mice

Developmental neuronal cell death is critically regulated by the pro-death protein Bax. Bax−/− mice exhibit increased neuron number, the elimination of several neural sex differences, and altered socio-sexual behaviors. Here we examined the effects of Bax gene deletion on anxiety and defensive behaviors by comparing the responses of male and female wildtype and Bax−/− mice to two different tests. On the elevated plus maze, Bax−/− mice of both sexes made more entries into and spent more time in the outer portion of open arms, indicating decreased anxiety compared to wildtype animals. Next, we exposed mice to two odors: trimethylthiazoline (TMT), an olfactory component of fox feces that rodents find aversive, and butyric acid (BA), an aversive odor without ecological significance. Each odor was presented individually and all animals were tested with both odors in a counterbalanced design. TMT was consistently more aversive than BA across a variety of behaviors (e.g., mice spent less time close to the odor source). Overall, Bax −/− mice showed fewer stretch approaches to both TMT and BA than wildtypes, but they avoided the odor source more (e.g., fewer contacts and less time spent in proximity). Finally, no effect of genotype was seen in baseline olfactory behavior; all mice were able to locate a buried food item, demonstrating that Bax−/− mice do not have impaired olfaction per se. Collectively, these data suggest a change in strategy with anxiety and defensive behaviors in Bax−/− mice, indicating that alterations in cell number affect more general mechanisms of fear and anxiety in addition to behaviors directly related to reproduction.

► Bax deletion results in increased neuron number in many phenotypic populations.
► Bax−/− mice show reduced anxiety based on elevated-plus maze performance.
► Bax−/− mice employ a different defensive profile in response to aversive odors.
► Supernumerary neurons in Bax−/− mice appear to influence fear and anxiety.