LOCI AFFECTING HYBRID STERILITY IN MICE

描述：雄性小鼠F_1代杂交获得杂种不育性 不同的物种或亚种是由基因决定的。杂交种不育 在(C57BL/6J x M.spretus)中，F1雄性涉及伪常染色体上的一个基因座 区域(PAR)是X和Y染色体片段之间的强制性配对 在减数分裂期间。在这些不育的男性中，X//Y发生分离， 性染色体不能正常分离。在之前的资金中 与近端Chr X杂交不育相关的第2个新基因座是 已确认身份。其中一个基因座Ihtw1是在一个同源菌株中发现的。 C57BL/6J.Hprts，包含14个地图单位，来自一个 C57BL/6背景。Ihtw1与较小的睾丸重量有关，并允许 部分生育，但只有一半的睾丸小管充满了 减数分裂细胞和发育中的精子，而其他的小管是空的。这个 Chr X近端的第二个新基因座阻止进入雄性减数分裂I 用回交雄性后代(C57BL/6J×M)发现。 Macedonicus)x C57BL/6J。一些携带Macedonicus的回交雄性 Chr-X末端的等位基因进入减数分裂，但表现为X//Y分离。 这项研究还在Chr17近端发现了一个可能相同的基因座 与先前描述的HST基因座有关联。 这项提议有两个主要目标。第一个目标是延长基因 分析鼠标的标准杆，并启动对此的物理分析 区域，使用先前的工作已经生成的大量资源 这笔赠款和本提案中所述的新资源。体能 PAR的结构将与重组频率和 与在男性和男性中发生的重组位置 F1雌性动物。其次，将对Ihtw1进行精细规划，并增加 将制造同源菌株来分离控制该病毒的基因 在最近分析的猕猴回交中发现的表型。 同源菌株表型的遗传分离是必要的 鉴定和克隆基因的第一步。这其中的每一个 基因至少有一个抑制子，基因实验被描述为 定位影响杂交不育的基因座的抑制子并确定 无论他们的行为是显性的还是隐性的。在上找到的轨迹 近端Chr X及其抑制子可能在导致 人类男性的不育症。

DESCRIPTION: Hybrid sterility in male mouse F1 hybrids obtained by crossing different species or subspecies is genetically determined. Hybrid sterility in (C57BL/6J x M. spretus)F1 males involves a locus in the pseudoautosomal region (PAR) were obligatory pairing between the X and Y chromosome takes place during meiosis. In these sterile males X//Y dissociation occurs and the sex chromosomes cannot segregate normally. In the pervious funding period two new loci associated with hybrid sterility on proximal Chr X were identified. One of these loci, Ihtw1, was found in a congenic strain C57BL/6J.Hprts, containing 14 map units from the M. spretus Chr X on a C57BL/6 background. Ihtw1 is associated with small testis weight and allows partial fertility, but only half of the testicular tubules are filled with meiotic cells and developing sperm, while the other tubules are empty. The second new locus also on proximal Chr X, prevents entry into male meiosis I and was found using the male progeny of the backcross, (C57BL/6J x M. macedonicus) x C57BL/6J. Some backcross males carrying M. Macedonicus alleles at the distal end of Chr X enter meiosis but show X//Y dissociation. This study also identified a locus on proximal Chr 17, that may be identical to the previously described Hst loci. This proposal has two major goals. The first goal is to extend the genetic analysis of the mouse PAR and to initiate a physical analysis of this region, using a number of resources already generated by earlier work on this grant and by new resources described in this proposal. The physical structure of the PAR will be correlated with recombination frequency and with the positions of recombination that have occurred in both male and female F1 animals. Second, Ihtw1 will be fine mapped and additional congenic strains will be made to isolate the genes controlling the phenotypes discovered in the recently analyzed M. macedonicus backcross. The genetic isolation of the phenotypes in congenic strains is a necessary first step toward identification and cloning of the genes. Each of these genes has at least one suppressor, and genetic experiments are described to map the suppressors for the loci affecting hybrid sterility and to determine whether they act in a dominant or recessive manner. The loci found on proximal Chr X and their suppressor may play a significant role in causing sterility in the human male.