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产生四个单倍体孢子或 配子。减数分裂缺陷导致不育、生育力降低和非整倍体。 非整倍体是流产和共同发育的主要原因 疾病，如唐氏综合症。由于这些破坏性影响，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，在酿酒酵母中，大量 有证据表明，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。因为在小鼠中，减数分裂 必须在多细胞和性二态性的背景下运作 系统中，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。使用比较遗传学和正向遗传学 方法，该提案的目标是初步表征减数分裂 小鼠体内的检查点，而人们对这些途径的了解要少得多。至 实现这一目标，假定的减数分裂检查点蛋白的功能， Rad24，将被删除。将创建双突变体以查看减数分裂是否 在假定的重组突变体和新的减数分裂突变体中发现了逮捕， 通过删除 Rad24 功能可以缓解这些问题。如果是这样，这将表明 Rad24 是小鼠减数分裂检查点的关键蛋白。此外，这将 提供有关引发减数分裂停滞的缺陷类型的信息 老鼠。最后，一种新的、潜在的减数分裂突变，Mei5，可能会导致 逃过减数分裂检查点机制检测的减数分裂缺陷，将被 表型特征和基因图谱。

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.