Elevated reactive aggression in forebrain‐specific Ccn2 knockout mice

Cellular communication network factor 2 (CCN2) is a matricellular protein that plays important roles in connective tissue. CCN2 is also expressed in the nervous system; however, its role is still unclear. To explore CCN2 function in the brain, we generated forebrain‐specific Ccn2 knockout (Fb Ccn2 KO) mice. In this study, we examined the behavioral phenotypes of Fb Ccn2 KO mice. Male mice lacking CCN2 in the forebrain exhibited normal locomotion, sensorimotor gating, and social behaviors but signs of anxiety and elevated reactive aggression. We checked the c‐fos expression in aggression‐related brain regions following the resident‐intruder task (RIT), an aggression test. RIT‐induced c‐fos levels in the medial amygdala (MeA) were higher in Fb Ccn2 −/− mice as compared to controls. However, in the prefrontal cortex, RIT‐induced c‐fos levels in Fb Ccn2 −/− mice were lower than controls. Our results suggested in male mice lacking CCN2 in the olfaction‐related regions, olfactory social cues elicit greater signals in the MeA, resulting in greater reactive aggression in the RIT. Further, lacking CCN2 in the prefrontal cortex, the major area related to inhibitory control and emotion regulation, may lead to signs of anxiety and the failure to suppress aggressive behaviors. Our model is useful in elaborating the mechanism underlying reactive aggression and therapeutic strategies.