Genetic Analysis of Nematode Behavior

线虫行为的遗传分析

• 批准号: 6921340
• 负责人: SCOTT W EMMONS
• 金额: $ 23.38万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6921340
• 关键词: Caenorhabditis elegans; behavior test; behavioral /social science research tag; behavioral genetics; ethology; gene environment interaction; gene expression; gene interaction; genetic mapping; genetic models; genetic screening; helminth genetics; histamine; libido; male; molecular cloning; motivation; mutant; neurotransmitters; octopamine; psychopharmacology; reproduction; serotonin; serotonin transporter; sex behavior; Caenorhabditis elegans; behavior test; behavioral /social science research tag; behavioral genetics; ethology; gene environment interaction; gene expression; gene interaction; genetic mapping; genetic models; genetic screening; helminth genetics; histamine; libido; male; molecular cloning; motivation; mutant; neurotransmitters; octopamine; psychopharmacology; reproduction; serotonin; serotonin transporter; sex behavior

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.

描述（由申请人提供）：本研究研究了男性性动机和行为的遗传基础。导致性繁殖的行为对于大多数动物物种的生存至关重要，但目前对神经系统如何产生适当的动机状态以及充满活力和完美的性行为的知之甚少。一种理解动物行为的方法是鉴定必需基因并研究其细胞表达模式和分子功能。为了鉴定男性性行为所需的基因，将在土壤圆形蠕虫Caenorhabditis秀丽隐杆线虫中鉴定出性行为的开胃阶段和完整阶段的突变体，这是一种明确定义的无脊椎动物遗传模型生物体。 初步研究已经建立了一种定量行为分析，用于成年秀丽隐杆线虫男性推定的伴侣搜索行为。该测定法被用来表明伴侣搜索行为的表达受到合适的伴侣的存在，营养状况以及生殖系统的信号。结果被解释为表明伴侣进行搜索是由神经系统的受调节状态增强的，我们将其定义为高等动物的性动机的线虫类似物。 将进行遗传筛选以识别两种类型的新突变体：男性无法表达伴侣搜索行为的突变体和男性表现出性欲却无法交配的突变体。确定的选择性基因将被分子克隆，并定义其产品的身份和表达模式。 在已经鉴定出的三个伴侣搜索缺陷的遗传基因座中，一个编码了5-羟色胺再摄取转运蛋白的秀丽隐杆线虫同源物，这是人类和氟西汀抗抑郁药的靶标。鉴于人类氟西汀给药引起的性功能障碍，这表明这些研究可能与理解人类的动机性行为有关，因此可能具有潜在的临床意义。