Deletion of corticotropin-releasing factor binding protein selectively impairs maternal, but not intermale aggression

Abstract

Corticotropin-releasing factor (CRF) binding protein (CRF-BP) is a secreted protein that acts to bind and limit the activity of the neuropeptides, CRF and urocortin (Ucn) 1. We previously selected for high maternal defense (protection of offspring) in mice and found CRF-BP to be elevated in the CNS of selected mice. We also previously determined that both CRF and Ucn 1 are potent inhibitors of offspring protection when administered centrally. Thus, elevated CRF-BP could promote defense by limiting endogenous actions of CRF or Ucn 1. To test this hypothesis, we crossed the deletion for CRF-BP into the mice selected for high maternal defense and evaluated offspring protection and other maternal behaviors. CRF-BP knockout (KO) mice exhibited significant deficits in maternal aggression relative to wild-type (WT) mice in three different measures. Other maternal features were almost identical between groups, including dam and pup weight, litter size, nursing time, and pup retrieval. Both groups performed similarly in a forced swim stress test and aggression in both groups was reduced following the swim test. Virgin KO female mice exhibited higher levels of anxiety-like behavior in terms of decreased time in the light portion of the light/dark box test. For males, no differences in light/dark box or swim test were found. However, increased anxiety-like behavior in male KO mice was identified in terms of contact and approach to a novel object both with and without previous exposure to the swim test. No differences in isolation induced resident intruder male aggression were found between groups. Together, these results indicate that loss of CRF-BP selectively impairs maternal, but not intermale aggression and that loss of the gene induces anxiety-like behavior in males and females, but there are sex differences in terms of how that anxiety is revealed.