Genetic basis of gonadal steroid-independent male social behavior

这项建议的首要目标是增加我们对调节基因表达的遗传机制的理解。 男性的社会行为我们关于社会行为的大部分知识都是基于 在大多数实验室中， 在野生啮齿类动物和哺乳动物中，雄性的社会行为发生在繁殖季节， 高度依赖于同时使用贡达尔类固醇。然而，在个人和 在不同的物种中，类固醇在男性社会行为中的依赖性是高度可变的，我们缺乏 关于这些行为的遗传基础的知识仍然是一个主要障碍， 了解人类男性的行为通常被认为是依赖于性腺类固醇。 为了研究这一点，所用的模型种属将是杂交B6D2F1雄性小鼠，其中大部分 在睾丸切除后很长一段时间内保留了完整的雄性社会和交配行为。我们有 完成了基因表达阵列的生物信息学分析，比较了已知关键位点的mRNA， 中介男性社会行为，内侧视前区和终纹床核，之间 杂交小鼠，坚持和那些停止互动后，共同体切除。我们的分析表明 6个新的复杂社会行为候选基因：S0D1、PTEN、SCN1A、IMPA1、APP、MART。所有六 基因是新的，如果没有这个微阵列， 分析.该提案的具体目的是验证微阵列分析的结果，然后测试 候选基因在性腺类固醇非依赖性男性社会行为中的作用。

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.