Recombination and meiotic progression in the mouse

小鼠的重组和减数分裂进展

• 批准号: 6640514
• 负责人: LAURA G REINHOLDT
• 金额: $ 4.16万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-15 至 2005-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6640514
• 关键词: DNA damage; DNA repair; Saccharomyces cerevisiae; cell cycle proteins; cytogenetics; developmental genetics; environmental toxicology; fungal proteins; gene mutation; gene targeting; genetic mapping; genetic recombination; genetically modified animals; laboratory mouse; meiosis; methylguanine DNA methyltransferase; mutant; protein structure function

DESCRIPTION (provided by applicant): Meiosis is the specialized cell division whereby one diploid cell divides twice to produce four haploid spores or gametes. Meiotic defects lead to sterility, reduced fertility and aneuploidy. Aneuploidy is a leading cause of miscarriage and common developmental disorders, like Down ?s syndrome. Because of these devastating effects, meiotic checkpoints help to arrest meiosis in response to defects that cause aneuploidy. For example, in the yeast, Saccharomyces cerevisiae, substantial evidence shows that recombination defects cause a meiotic arrest, which is dependent on the DNA damage checkpoint protein, RAD24. Because in mice, meiosis must operate within the context of a multi-cellular and sexually dimorphic system, it is likely that a large number of novel mammalian meiotic genes exist to accommodate this system. Using both comparative and forward genetics approaches, this goal of this proposal is to initially characterize a meiotic checkpoint in mice, where significantly less is known about these pathways. To achieve this goal, the function of a putative meiotic checkpoint protein, Rad24, will be removed. Double mutants will be created to see if the meiotic arrests found in a putative recombination mutant and in a novel meiotic mutant, are alleviated by the removal of Rad24 function. If so, this will show that Rad24 is a key meiotic checkpoint protein in mice. In addition, this will provide information as to the types of defects that trigger meiotic arrest in mice. Finally, a new, potentially meiotic mutation, Mei5, which may cause a meiotic defect that escapes detection by meiotic checkpoint mechanisms, will be phenotypically characterized and genetically mapped.

描述（由申请人提供）：减数分裂是专门的细胞部门 因此，一个二倍体细胞划分两次，产生四个单倍体孢子或 配子。减数分裂缺陷会导致不育，降低生育能力和非整倍性。 非整倍性是流产和共同发展的主要原因 疾病，例如唐氏综合症。由于这些毁灭性的效果，减数分裂 检查点有助于阻止减数分裂，以应对导致的缺陷 非整倍性。例如，在酵母中，酿酒酵母，大量 有证据表明，重组缺陷会导致减数分裂逮捕，即 取决于DNA损伤检查点蛋白RAD24。因为在老鼠中，减数分裂 必须在多态和性二态的背景下进行操作 系统，可能存在大量新型的哺乳动物减数分裂基因 适应该系统。同时使用比较和正向遗传学 方法是，该提议的这个目标是最初描述减数分裂 小鼠的检查点，在这些途径中，了解这些途径的了解要少得多。到 实现此目标，假定的减数分裂检查点蛋白的功能， RAD24将被删除。将创建双重突变体，以查看是否减数分裂 在推定的重组突变体和新型的减数分裂突变体中发现的逮捕， 通过去除RAD24功能来缓解。如果是这样，这将表明 RAD24是小鼠中的关键减数分裂检查点蛋白。此外，这将 提供有关触发减数分裂逮捕的缺陷类型的信息 老鼠。最后，一个新的，可能是减数分裂突变，mei5，这可能会导致 通过减数分裂检查点机制逃避检测的减数分裂缺陷将是 表型表征和遗传映射。