THE ROLE OF HORMAD1 IN GERM CELL DEVELOPMENT AND MEIOSIS

描述(由申请人提供)：研究人员对了解生殖细胞发育所必需的特定遗传途径很感兴趣。他们发现了一种以前未知的基因Hormad1，它编码一种带有Horma结构域的蛋白质。HORMA是在减数分裂和有丝分裂纺锤体检查点、染色体突触和DNA修复等蛋白质中遇到的一个特殊结构域。在酵母、线虫和植物中描述了在减数分裂中起关键作用的Horma结构域蛋白，包括Hop1p、Red1p、HIM-3和Asy1。减数分裂特异的Horma结构域蛋白在染色体的联会、分离和重组过程中起着关键作用。目前还没有已知的哺乳动物减数分裂特异的Horma结构域蛋白，也没有已知的哺乳动物与Hop1p、Red1p、HIM-3或Asy1的同源物。研究人员推测，Hormad1编码哺乳动物减数分裂特有的Horma结构域蛋白，并在哺乳动物生殖细胞发育和减数分裂中发挥关键功能。他们的初步结果表明，Hormad1优先在生殖细胞中表达，Hormad1缺陷的小鼠是不育和性腺功能低下的。他们建议开发针对HORMAD1的抗体来研究其表达，然后确定细胞和减数分裂染色体的定位。此外，他们将使用新创造的Hormad1基因敲除小鼠来描述导致男性和女性不育的性腺病理的发病情况。这些研究对于开始了解高度保守的HORMAD1蛋白在生殖细胞发育和减数分裂I中的功能将是重要的。 项目相关性：研究人员发现了一个新的基因，Hormad1，它编码一种可能在哺乳动物减数分裂中起重要作用的蛋白质。Hormad1功能缺失会导致不孕。他们将研究Hormad1小鼠的不孕症是否是生殖细胞功能异常造成的。

DESCRIPTION (Provided by Applicant): The investigators are interested in understanding specific genetic pathways that are essential for germ cell development. They discovered a previously unknown gene, Hormad1, which encodes a protein with HORMA domain. HORMA is a specialized domain encountered in proteins functioning in meiotic and mitotic spindle checkpoints, chromosome synapsis, and DNA repair. The HORMA domain proteins critical in meiosis were described in yeast, nematodes, and plants, and include Hop1p, Red1p, Him-3, and Asy1. Meiosis specific HORMA domain proteins are critical in synapsis, segregation, and recombination of chromosomes. There are no known meiosis specific HORMA domain proteins in mammals, and no known mammalian homologues to Hop1p, Red1p, Him-3, or Asy1. The investigators hypothesize that Hormad1 encodes a meiosis specific HORMA domain protein in mammals and that it plays critical functions in mammalian germ cell development and meiosis. Their preliminary results suggest that Hormad1 is preferentially expressed in germ cells, and that Hormad1 deficient mice are infertile and hypogonadal. They propose to develop antibodies against HORMAD1 to study its expression, and then determine the cellular as well as meiotic chromosome localization. In addition, they will use the newly created Hormad1 knock-out mouse to delineate the onset of gonadal pathology that leads to male and female infertility. These studies will be important to begin understanding the function of the highly conserved HORMAD1 protein in germ cell development and meiosis I. PROJECT RELEVANCE: The investigators identified a novel gene, Hormad1, which encodes a protein likely to be important in mammalian meiosis. Absence of Hormad1 function causes infertility. They will study whether infertility in Hormad1 mice results from abnormal germ cell function.