THE ROLE OF HORMAD1 IN GERM CELL DEVELOPMENT AND MEIOSIS

HORMAD1 在生殖细胞发育和减数分裂中的作用

• 批准号: 7700751
• 负责人: ALEKSANDAR RAJKOVIC
• 金额: $ 7.93万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-04 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7700751
• 关键词: Aneuploidy; Antibodies; Binding; Cell Survival; Cell physiology; Cellular biology; Chromosome Pairing; Chromosome abnormality; Chromosomes; Complex; DNA Repair; Data; Development; Embryo; Female; Female infertility; Genes; Genetic; Genetic Recombination; Germ Cells; Homologous Gene; Infertility; Knockout Mice; Mammals; Meiosis; Mitosis; Mitotic/Spindle Checkpoint; Mus; Names; Nematoda; Ovary; Pathology; Pathway interactions; Pattern; Plants; Play; Proteins; Reproduction; Research Personnel; Role; Synaptonemal Complex; Tertiary Protein Structure; Testis; Yeasts; fetal; gene function; in vivo; insight; interest; male; neonatal death; novel; offspring; postnatal; protein expression; protein function; segregation

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.

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感兴趣。他们发现了一种以前不为人知的基因，Hormad1，它编码一种具有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修复中遇到的一个特殊结构域。在酵母、线虫和植物中发现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。减数分裂特异性HORMA结构域蛋白在染色体的突触、分离和重组中起关键作用。在哺乳动物中没有已知的减数分裂特异性HORMA结构域蛋白，也没有已知的Hop1p、Red1p、Him-3或Asy1的哺乳动物同源物。研究人员推测，Hormad1编码哺乳动物减数分裂特异性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作用。他们的初步结果表明，Hormad1优先在生殖细胞中表达，并且Hormad1缺陷的小鼠不育和性腺功能低下。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，他们将使用新创建的Hormad1敲除小鼠来描述导致男性和女性不育的性腺病理的发病。这些研究将对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中的功能具有重要意义。