Genetic basis of gonadal steroid-independent male social behavior

这项建议的首要目的是增加我们对基因调控机制的理解 男性的社交行为。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，类固醇激素与行为之间的关系被描绘出来 野生啮齿动物和哺乳动物，雄性的社会行为发生在繁殖季节，是 高度依赖贡达尔类固醇的同时可获得性。然而，在个人和个人之间 在不同物种中，男性社交行为对类固醇的依赖程度是高度可变的，而我们缺乏 关于这些行为的遗传基础的知识仍然是 理解通常被认为依赖性腺类固醇的人类男性行为。 为了调查这一点，所使用的模式物种将是杂交的B6D2F1雄性小鼠，其中占很大比例 在兰花切除后很长一段时间内保留了完整的雄性社交和交配行为。我们有 完成了对基因表达阵列的生物信息学分析，比较了已知的关键位点的mRNA 调节男性社会行为，视前内侧区和终纹床核，在 持续存在的杂交小鼠和那些在兰花切除后停止社交互动的小鼠。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。所有六个人 基因是新的，如果没有这个微阵列，就不会涉及到这些社会行为 分析。这项建议的具体目的是验证微阵列分析的结果，然后进行测试 候选基因在性腺激素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.