The overriding aim of this proposal is to increase our understanding of the genetic mechanisms regulating male social behaviors. Most of our knowledge concerning social behavior has been based on classic work in which the relationship between the steroid hormones and behaviors were delineated: in most laboratory rodent species and mammals in the wild, male social behavior occurs during the breeding season and is highly dependent upon the concurrent availability of gondal steroids. However, between individuals and across species, the dependence of steroids in male social behavior is highly variable, and our lack of knowledge concerning the genetic underpinnings of these behaviors remains a major obstacle to understanding human male behaviors normally thought to be dependent on gonadal steroids. To investigate this, the model species used will be hybrid B6D2F1 male mice in which a large proportion retains the complete repertoire of male social and copulatory behaviors long after orchidectomy. We have completed a bioinformatic analysis of gene expression arrays comparing mRNA from critical sites known to mediate male social behavior, the medial preoptic area and the bed nucleus of the stria terminalis, between hybrid mice that persist and those that cease to interact socially after orchidectomy. Our analysis has linked six novel candidate genes to complex social behaviors: S0D1, PTEN, SCN1A, IMPA1, APP, MART. All six genes are novel and would not have been implicated in these social behaviors without this microarray analysis.
The specific aims of this proposal are to validate the results of the microarray analysis and then test the role of the candidate genes in gonadal steroid-independent male social behavior.
Social relationships are important for quality of life for people at all ages, but especially in senior citizens and patient populations. Groups that would benefit from this research include aging men experiencing declining testosterone concentrations and the vast majority of prostate cancer survivors that report dissatisfaction with the quality of their intimate relationships. It is our hope that this research may ultimately be utilized in the near future to develop new treatments for ererctile dysfunction in men.
