Sex chromosome effects on neural and behavioral differentiation

描述（由申请人提供）：在不同的文化和物种中，男性和女性在攻击性表达和父母养育行为方面存在差异。在两性中，男性几乎普遍更具攻击性，更不像父母。大多数（但不是全部）行为上的性别差异可归因于雄性和雌性发育过程中类固醇激素浓度的差异。男性和女性之间差异的另一个潜在来源是存在于性染色体上的基因。一种性腺和染色体性别分离的转基因小鼠模型被用来检验这一假设。两种行为差异可归因于性染色体互补，独立于性腺性别，是攻击性攻击和幼犬取回行为。迄今为止研究的一个神经因素与这些行为有关；侧隔抗利尿激素免疫反应性。在这项新的拨款申请中，将研究这些性别差异的遗传基础。将进行一系列的基因、行为和药理学实验。首先，将产生一个独特的小鼠杂交，以确定是XX的X基因的两个拷贝，还是XY雌性中Y染色体基因的存在导致了XX和XY个体的行为差异。接下来将进行一系列研究，以更深入地研究这两种令人感兴趣的行为，并量化大脑中与性染色体互补有关的其他性别差异。为了确定发育过程中雄激素的暴露是否与性染色体基因相互作用，新生儿刚出生时雄激素就会被阻断。利用不能产生内源性雌激素的敲除小鼠的基因方法也将被使用。神经加压素将被独立于性染色体操纵，以确定这种神经肽如何以及是否与攻击行为有关。总之，这项工作将增加我们对这组重要的两性二态基因及其基因产物功能的认识。这项工作还将丰富和告知我们关于正常人群和临床人群性别差异的知识。

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.