Sex chromosome effects on neural and behavioral differentiation

性染色体对神经和行为分化的影响

• 批准号: 7611868
• 负责人: Emilie F. Rissman
• 金额: $ 4.95万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7611868
• 关键词: Address; Adult; Aggressive behavior; Androgen Receptor; Androgens; Applications Grants; Aromatase; Behavior; Behavioral; Behavioral Genetics; Birth; Brain; Breeding; Castration; Cell Nucleus; Chromosomes, Human, Pair 10; Clinical; Condition; Data; Depth; Development; Dopaminergic Cell; Dose; Enzyme Gene; Estradiol; Estrogens; Exposure to; Female; Feminine; Fiber; Genes; Genetic; Gonadal Steroid Hormones; Gonadal structure; Hormonal; Individual; Knock-out; Knockout Mice; Knowledge; Laboratory mice; Lateral; Link; Masculine; Medial; Mouse Strains; Mus; Mutant Strains Mice; Mutate; Mutation; Neonatal; Neurons; Neuropeptides; Numbers; Ovary; Pattern; Perinatal; Pharmacology; Phenotype; Ploidies; Population; Production; Proteins; Receptor Cell; Regulation; Reporting; Research Personnel; Role; Series; Sex Characteristics; Sex Chromosomes; Source; Staging; Steroids; Structure of terminal stria nuclei of preoptic region; Sum; System; Testing; Testis; Testosterone; Time; Transgenes; Transgenic Organisms; Ursidae Family; Vasopressin Receptor; Vasopressins; Work; Y Chromosome; calbindin; critical developmental period; density; immunoreactivity; interest; male; mouse model; neonate; neurodevelopment; novel; programs; pup; relating to nervous system; research study; sex; sexual dimorphism; sry Genes; steroid hormone

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.

在不同的文化和物种中，雄性和雌性在攻击性和父母教养的表达上是不同的。 养育行为在这两者中，雄性几乎普遍更具侵略性， 性别大多数，但不是全部，性别差异的行为可以归因于不同的类固醇 雄性和雌性发育过程中的激素浓度。另一个潜在的分歧来源 男性和女性之间的区别在于性染色体上的基因。转基因小鼠模型 其中性腺和染色体的性别是分离的，正被用来检验这一假设。两 行为差异可归因于性染色体的补充，独立于性腺性别， 是攻击性的攻击和幼犬的寻回行为迄今为止，一个神经因素与以下因素相关： 这些行为;加压素免疫反应在外侧隔。在这项新的拨款申请中， 将对这些性别差异的基础进行调查。一系列的遗传的，行为的， 将进行药理学实验。首先，将产生唯一的小鼠杂交以确定是否 对于XX，X基因的两个拷贝，或者XY女性中Y染色体基因的存在导致 XX和XY个体之间的行为差异。接下来将进行一系列研究， 更深入地研究这两种感兴趣的行为，并量化大脑中其他性别的差异， 性染色体补体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，雄激素将在新生儿出生后被阻断。一种遗传学方法， 利用不能产生内源性雌激素的基因敲除小鼠。 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一点。 神经肽与攻击行为有关。总之，这项工作将增加我们对 这组重要的两性异形基因及其基因产物的功能。这项工作也将丰富 并告知我们在正常和临床人群中的性别差异知识。