The function of Runx1 in the ovary

Runx1在卵巢中的功能

• 批准号: 7018011
• 负责人: MISUNG JO
• 金额: $ 7.32万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7018011
• 关键词: corpus luteum; developmental genetics; fertility; gene expression profiling; gene induction /repression; genetically modified animals; graafian follicles; granulosa cell; hormone regulation /control mechanism; laboratory mouse; luteinizing hormone; ovary; ovulation; protein structure function; recombinase; transcription factor

DESCRIPTION (provided by applicant): The goal of the present proposal is to elucidate the role of Runx1, a nuclear transcription factor, in the ovary. We have recently identified that this transcription factor is dramatically and transiently induced in granulosa cells of periovulatory follicles after the LH [luteinizing hormone] surge. The periovulatory follicle undergoes rapid changes in the expression patterns of a myriad of genes to bring about ovulation and luteinization. Therefore, transcriptional regulators induced by the LH surge are believed to play an essential role in the ovulatory process and luteinization. We have preliminary data showing that knockdown of the LH-induced Runx1 expression in periovulatory granulosa cells resulted in a decrease in progesterone production, implicating the involvement of Runx1 in luteinization. We also found that Runx1 expression is regulated by the activation of the progesterone receptor and EGF [epidermal growth factor]-receptor, two known key mediators for the ovulatory process. Based on these novel findings, we hypothesize that Runx1 plays an important role(s) in ovulation and luteinization. The goal of this proposal is to: 1) demonstrate that the induction of Runx1 in periovulatory granulosa cells is essential for successful ovulation and luteinization and 2) determine the specific role(s) of Runx1 in periovulatory granulosa cells. To accomplish this goal, we will generate mice lacking functional Runx1 specifically in granulosa cells, and then examine the ovarian phenotype of these mutant mice (Specific Aim 1). Using the granulosa cell-specific Runx1 null mice, we will identify the genes down-stream of Runx1 action in periovulatory granulosa cells (Specific Aim 2). Information derived from this proposal will provide new insight into the mechanism(s) involved in ovulation and corpus luteum formation. Such knowledge can be applied for promoting or inhibiting these critical facets of ovarian physiology, thereby allowing us to better manage fertility, infertility, and ovarian-based disorders.

描述（由申请人提供）：本提案的目的是阐明卵巢中核转录因子Runx1的作用。我们最近确定，在LH [黄体生成激素]激增后，该转录因子在卵泡周围卵泡的颗粒细胞中急剧，瞬时诱导。卵形卵泡周围经历了无数基因的表达模式的快速变化，以引起排卵和黄体化。因此，据信由LH激增引起的转录调节剂在排卵过程和黄体化过程中起着至关重要的作用。我们的初步数据表明，在卵巢颗粒细胞中敲低LH诱导的Runx1表达会导致孕激素产生的降低，这暗示Runx1参与了黄体化。我们还发现，Runx1表达受孕酮受体和EGF [表皮生长因子] - 受体的激活，这是两个已知的排卵过程的关键介体。基于这些新颖的发现，我们假设Runx1在排卵和黄体化中起重要作用。该提议的目的是：1）证明Runx1在卵巢颗粒细胞中的诱导对于成功排卵和黄体化至关重要，并且2）确定Runx1在卵巢颗粒细胞中的特定作用。为了实现这一目标，我们将生成缺乏功能性RUNX1的小鼠，专门在颗粒细胞中，然后检查这些突变小鼠的卵巢表型（特定目标1）。使用颗粒细胞特异性RUNX1 NULL小鼠，我们将在卵巢颗粒细胞中识别Runx1作用的下游基因（特定的AIM 2）。从该提案中得出的信息将提供有关排卵和叶黄素形成的机制的新见解。这些知识可用于促进或抑制卵巢生理的这些关键方面，从而使我们能够更好地管理生育能力，不育和基于卵巢疾病。