Recombination and meiotic progression in the mouse

描述（由申请人提供）：减数分裂是专门的细胞分裂 其中一个二倍体细胞分裂两次以产生四个单倍体孢子， 配子减数分裂缺陷导致不育、生育力降低和非整倍体。 非整倍体是流产和常见发育不良的主要原因。 比如唐氏症s综合征。由于这些破坏性的影响，减数分裂 检查点有助于阻止减数分裂， 非整倍性例如，在酵母、酿酒酵母中， 有证据表明，重组缺陷导致减数分裂停滞， 依赖于DNA损伤检查点蛋白，RAD24。因为在老鼠体内，减数分裂 必须在一个多细胞和两性异形的环境中运作 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。利用比较遗传学和正向遗传学 方法，这个建议的目标是初步表征减数分裂 小鼠中的检查点，其中对这些途径的了解明显较少。到 实现这一目标，一个假定的减数分裂检查点蛋白的功能， 第24章将被淘汰双突变体将被创造出来，看看减数分裂是否 在假定的重组突变体和新的减数分裂突变体中发现的停滞， 通过移除Rad24功能来缓解。如果是这样，这将表明， Rad24是小鼠中关键的减数分裂检查点蛋白。此外，这将 提供了关于引发减数分裂停滞的缺陷类型的信息， 小鼠最后，一个新的，潜在的减数分裂突变，Mei5，这可能会导致一个新的基因突变。 逃避减数分裂检查点机制检测的减数分裂缺陷，将被 表型特征和遗传图谱。

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.