Recombination and meiotic progression in the mouse

小鼠的重组和减数分裂进展

• 批准号: 6551512
• 负责人: LAURA G REINHOLDT
• 金额: $ 3.66万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6551512
• 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(申请人提供)：减数分裂是特化的细胞分裂 其中一个二倍体细胞分裂两次，产生四个单倍体孢子或 配子。减数分裂缺陷会导致不育、生育能力下降和非整倍体。 非整倍体是流产和共同发育的主要原因 疾病，如唐氏综合症？S综合征。由于这些毁灭性的影响，减数分裂 检查点有助于阻止减数分裂，以应对导致 非整倍体。例如，在酵母中，酿酒酵母中，大量 证据表明，重组缺陷会导致减数分裂停滞，这是 依赖于DNA损伤检查点蛋白RAD24。因为在小鼠身上，减数分裂 必须在多细胞和性二型的背景下运作 系统，很可能存在大量新的哺乳动物减数分裂基因 来适应这个系统。同时使用比较遗传学和正向遗传学 方法，这项建议的目标是初步表征减数分裂 小鼠中的检查点，对这些通路的了解明显较少。至 为了实现这一目标，推测的减数分裂检查点蛋白的功能， RAD24，将被移除。将创造双重突变体，看看减数分裂是否 在一个假定的重组突变体和一个新的减数分裂突变体中发现的停滞， 通过移除Rad24函数而得到缓解。如果是这样，这将表明 Rad24是小鼠体内一个关键的减数分裂检查点蛋白。此外，这将是 提供关于引起减数分裂停止的缺陷类型的信息 老鼠。最后，一个新的，潜在的减数分裂突变，Mei5，可能导致 通过减数分裂检查点机制逃脱检测的减数分裂缺陷将是 表型特征和遗传图谱。