Reproductive Defects in the Clock Mutant Mouse

时钟突变小鼠的生殖缺陷

• 批准号: 6913595
• 负责人: BROOKE H MILLER
• 金额: $ 2.8万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2005-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6913595
• 关键词: biological clocks; circadian rhythms; cues; enzyme linked immunosorbent assay; female reproductive system disorder; gene expression; genetically modified animals; gestational age; hormone regulation /control mechanism; hypothalamic pituitary axis; laboratory mouse; luteinizing hormone; pituitary gonadal axis; predoctoral investigator; pregnancy disorder; prolactin; suprachiasmatic nucleus; vasopressins

DESCRIPTION (provided by applicant): A self-sustaining molecular pacemaker within the hypothalamus allows organisms to organize physiology and behavior around the light-dark cycle. In mammals, the CLOCK protein is an essential component of this pacemaker. A mouse strain with a dominant negative mutation in the Clock gene displays lengthened and/or arrhythmic locomotor activity in the absence of entraining cues, and we have recently determined that this strain also has pleiotropic reproductive defects. Female Clock homozygous mice display altered luteinizing hormone (LH) release irregular estrous cycles, and mid-gestational pregnancy failure. In the present proposal, we hypothesize that both the estrous cyclicity and gestational defects are due to altered output from the central pacemaker to the neurons responsible for controlling LH and prolactin release, respectively. We propose to identify the nature of the circadian output signal to these neurons, and to test this hypothesis by manipulating the candidate output signal in wild type and mutant animals.

描述（由申请人提供）：下丘脑内的自我维持分子起搏器允许生物体围绕明暗周期组织生理和行为。在哺乳动物中，CLOCK蛋白是这种起搏器的重要组成部分。在时钟基因中具有显性负突变的小鼠品系在没有夹带线索的情况下显示延长的和/或自发的运动活动，并且我们最近确定该品系也具有多效性生殖缺陷。雌性Clock纯合子小鼠表现出改变的促黄体生成激素（LH）释放，不规则的发情周期，以及妊娠中期妊娠失败。在本建议中，我们假设，这两个动情周期和妊娠缺陷是由于改变输出从中央起搏器的神经元负责控制LH和催乳素释放，分别。我们建议确定这些神经元的昼夜输出信号的性质，并通过操纵野生型和突变动物的候选输出信号来测试这一假设。