Sex chromosome effects on neural and behavioral differentiation

在不同的文化和物种中，男性和女性在攻击性和父母的表达上是不同的 养成行为。在两者中，男性几乎普遍是更具攻击性的，而不太像父母 性别。大多数但不是全部的性别行为差异可以归因于类固醇的差异 男性和女性发育过程中的激素浓度。另一个潜在的分歧来源 位于男性和女性之间的是位于性染色体上的基因。一种转基因小鼠模型 其中性腺和染色体的性行为是分离的，用来检验这一假设。二 可以归因于性染色体互补的行为差异，与性腺性别无关， 是进攻性攻击性和幼犬追回行为。到目前为止，研究的一个神经因素与 这些行为；外侧隔内的加压素免疫反应。在这项新的拨款申请中，基因 这些性别差异的基础将被调查。一系列的遗传、行为和 将进行药理实验。首先，将生成一个唯一的鼠标交叉以确定 在XX病例中X基因的两个副本，或者在XY女性中Y染色体基因的存在导致 XX和XY个体的行为差异。接下来，我们将进行一系列研究来检验 这两种感兴趣的行为更深入，并量化大脑中其他性别差异与 性染色体互补。为了确定在发育过程中暴露于雄激素是否与 性染色体基因，雄激素在新生儿出生后就会被阻断。一种遗传方法， 利用不能产生内源性雌激素的基因敲除小鼠也将被使用。 神经加压素将独立于性染色体进行操作，以确定如何以及是否这样做 神经肽与攻击性行为有关。总之，这项工作将增加我们对 这组重要的性二态基因及其基因产物的功能。这项工作也将丰富 并让我们了解正常人群和临床人群中的性别差异。

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 retreival 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 chromsome 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 neuropeptides 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.