Sex chromosome effects on neural and behavioral differentiation

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DESCRIPTION (provided by applicant): Across cultures, and species, males and females differ in the expression of aggression and parental nurturing behavior. Males are nearly universally the more aggressive, and the less parental, of the two sexes. The majority, but not all, sex differences in behavior can be attributed to differences in steroid hormone concentrations during development in males and females. Another potential source of differences between males and females are the genes that reside on the sex chromosomes. A transgenic mouse model in which gonadal and chromosomal sex are uncoupled is being employed to test this hypothesis. Two behavioral differences that can be attributed to sex chromosome complement, independent of gonadal sex, are offensive aggression and pup retrieval behavior. One neural factor examined to date is correlated with these behaviors; vasopressin immunoreactivity in the lateral septum. In this new grant application the genetic underpinnings of these sex differences will be investigated. A series of genetic, behavioral, and pharmacological experiments will be conducted. First a unique mouse cross will be produced to determine if two copies of the X genes in the case of XX, or the presence of Y chromosome genes in XY females causes the differences between behaviors in XX and XY individuals. Next a set of studies will be done to examine the two behaviors of interest in more depth, and to quantify other sex differences in the brain in relation to sex chromosome complement. To determine if the exposure to androgens during development interacts with sex chromosome genes, androgens will be blocked in neonates just after birth. A genetic approach that takes advantage of a knock out mouse that cannot produce endogenous estrogens will be used as well. Neural vasopressin will be manipulated independently of sex chromosomes to determine how and if this neuropeptide is related to aggressive behavior. In sum this work will increase our understanding of the function of this important group of sexual dimorphic genes and their gene products. The work will also enrich and inform our knowledge of sex differences in both normal and clinical populations.