Ephrin-A5 regulates inter-male aggression in mice

• Offensive and defensive aggression were studied in ephrin-A5 mutant (ephrin-A5−/−) mice.
• In the resident-intruder test for offensive aggression, ephrin-A5−/− mice exhibit severe reduction in aggression toward an intruder male.
• Defensive aggression in the form of target biting was higher in ephrin-A5−/− mice.
• Olfaction and testosterone levels were comparable between mutant and wild-type controls.

The Eph family of receptor tyrosine kinases play key roles in both the patterning of the developing nervous system and neural plasticity in the mature brain. To determine functions of ephrin-A5, a GPI-linked ligand to the Eph receptors, in animal behavior regulations, we examined effects of its inactivation on male mouse aggression. When tested in the resident-intruder paradigm for offensive aggression, ephrin-A5-mutant animals (ephrin-A5−/−) exhibited severe reduction in conspecific aggression compared to wild-type controls. On the contrary, defensive aggression in the form of target biting was higher in ephrin-A5−/− mice, indicating that the mutant mice are capable of attacking behavior. In addition, given the critical role of olfaction in aggressive behavior, we examined the ability of the ephrin-A5−/− mice to smell and found no differences between the mutant and control animals. Testosterone levels in the mutant mice were also found to be within the normal range. Taken together, our data reveal a new role of ephrin-A5 in the regulation of aggressive behavior in mice.