Does volized mouse become more romantic? Transcriptional lability of brain oxytocin receptor (Oxtr) generates diversity in brain Oxtr distribution and social behaviors

Although oxytocin (Oxt) is expressed in a highly conserved neuroanatomical pattern among vertebrates, brain OXT receptor (Oxtr) distribution is highly variable across species and associated with species-typical social behavior. Genetic mechanisms leading to diversity in brain Oxtr expression, and a causal link between brain Oxtr expression and social behaviors have not been demonstrated. Monogamous prairie voles and promiscuous mice have different brain Oxtr distribution. Here, eight independent “volized” transgenic prairie vole-Oxtr (pvOxtr) mouse lines were created carrying the Oxtr locus with the entire intergenic region (~160 kb). Remarkably, each line displayed a unique brain Oxtr expression pattern, but similar expression in mammary tissue. Moreover, “volized” mouse lines with different Oxtr expression patterns showed differences in partner preference and parental behaviors. These results, together with 3D-choromatin structure analysis, suggest that transcriptional sensitivity to long-distance interactions between proximal regulatory elements and distal sequences may contribute to “lability” of brain Oxtr expression, which in turn may lead to diversity of social behaviors.