Protein profiles from used nesting material, saliva, and urine correspond with social behavior in group housed male mice, Mus musculus.

Current understanding of how odors impact intra-sex social behavior is based on those that increase intermale aggression. Yet, odors are often promoted to reduce fighting among male laboratory mice. It has been shown that a cage of male mice contains many proteins used for identification purposes. However, it is unknown if these proteins relate to social behavior or if they are uniformly produced across strains. This study aimed to compare proteomes from used nesting material and three sources (sweat, saliva, and urine) from three strains and compare levels of known protein odors with rates of social behavior. Used nesting material samples from each cage were analyzed using LC-MS/MS. Sweat, saliva, and urine samples from each cage's dominant and subordinate mouse were also analyzed. Proteomes were assessed using principal component analyses and compared to behavior by calculating correlation coefficients between PC scores and behavior proportions. Twenty-one proteins from nesting material either correlated with affiliative behavior or negatively correlated with aggression. Notably, proteins from the major urinary protein family, odorant binding protein family, and secretoglobin family displayed at least one of these patterns, making them candidates for future work. These findings provide preliminary information about how proteins can influence male mouse behavior. SIGNIFICANCE: Research on how olfactory signals influence same sex social behavior is primarily limited to those that promote intermale aggression. However, exploring how olfaction modulates a more diverse behavioral repertoire will improve our foundational understanding of this sensory modality. In this proteome analysis we identified a short list of protein signals that correspond to lower rates of aggression and higher rates of socio-positive behavior. While this study is only correlational, it sets a foundation for future work that can identify protein signals that directly influence social behavior and potentially identify new murine pheromones.