Genetic Analysis of Nematode Behavior

描述(申请人提供)：本研究调查男性性动机和性行为的遗传基础。导致有性繁殖的行为对大多数动物物种的生存是必不可少的，但目前人们对神经系统如何产生适当的动机状态以及食欲和完成性行为知之甚少。理解动物行为的一种方法是识别必要的基因，并研究它们的细胞表达模式和分子功能。为了确定男性性行为所需的基因，将在土壤圆虫秀丽线虫(一种明确定义的无脊椎动物遗传模式生物)中发现在性行为的食欲和成熟阶段都有缺陷的突变体。 初步研究已经建立了一种对雄性线虫成虫可能的寻找配偶行为的定量行为分析。这种分析已经被用来表明，寻找配偶行为的表达受到合适配偶的存在或不存在、营养状况和生殖系统信号的调节。研究结果被解释为，神经系统的调节状态增强了寻找配偶的能力，我们将其定义为高等动物性冲动激励状态的线虫类似物。 将进行基因筛选，以识别两种类型的新突变：一种是雄性不能表现出寻找配偶的行为的突变，另一种是雄性表现出性冲动但无法交配的突变。识别的选择性基因将被分子克隆，并定义其产物的特性和表达模式。 在已经确定的三个交配搜索缺陷遗传基因座中，一个编码线虫5-羟色胺再摄取转运体的同源基因，这是氟西汀抗抑郁药在人类和线虫中的靶标。鉴于氟西汀在人体内引起的性功能障碍，这一结果表明，这些研究可能与理解人类动机性行为有关，因此可能具有潜在的临床意义。

DESCRIPTION (provided by applicant): This research investigates the genetic basis of male sexual motivation and behavior. Behaviors leading to sexual reproduction are essential for the survival of most animal species, yet little is presently known about how the nervous system generates appropriate motivational states and appetitive and consummatory sexual behaviors. One approach to understanding animal behavior is to identify essential genes and study their cellular expression patterns and molecular functions. In order to identify genes required for male sexual behavior, mutants defective in both appetitive and consummatory phases of sexual behavior will be identified in the soil round worm Caenorhabditis elegans, a well-defined invertebrate genetic model organism. Preliminary studies have established a quantitative behavioral assay for a putative mate-searching behavior of the adult C. elegans male. The assay has been used to show that expression of mate-searching behavior is regulated by presence or absence of suitable mates, nutritional status, and signals from the reproductive system. The results are interpreted to indicate that mate-searching is potentiated by a regulated state of the nervous system that we define as the nematode analog of a sex drive motivational state of higher animals. Genetic screens will be performed to identify new mutants of two types: mutants in which males fail to express mate-searching behavior and mutants in which males exhibit sex drive yet fail to copulate. Selective genes identified will be molecularly cloned and the identity and expression patterns of their products defined. Among three mate-searching-defective genetic loci already identified, one encodes the C. elegans homolog of the serotonin reuptake transporter, the target in both humans and nematodes of fluoxetine antidepressants. In view of the sexual dysfunction caused by fluoxetine administration in humans, this result suggests that these studies may have relevance to understanding motivated sexual behavior in humans and thus may have potential clinical implications.