LOCI AFFECTING HYBRID STERILITY IN MICE

描述：通过杂交获得的雄性小鼠F1杂种的杂种不育性 不同的物种或亚种是由基因决定的。 杂种不育性 在（C57BL/6J x M. spretus）F1雄性涉及假常染色体的一个位点， PAR区是X和Y染色体之间的强制配对区 在减数分裂中的位置。 在这些不育雄性中，X//Y解离发生， 性染色体不能正常分离。 在过去的资金 在近端染色体X上发现了两个与杂种不育相关的新位点， 鉴定 其中一个位点Ihtw 1在一个同源株中发现 C57BL/6J.Hprts，含M. spretus Chr X on a C57 BL/6背景。 IHTW 1与小睾丸重量相关， 部分生育能力，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，而其他小管是空的。 的 第二个新的基因座也在近端染色体X上，阻止进入雄性减数分裂I 并且使用回交的雄性后代（C57 BL/6 J × M）发现。 macedonicus）x C57BL/6J. 一些回交雄性携带M。马其顿人 在Chr X末端的等位基因进入减数分裂，但显示X//Y解离。 这项研究还确定了近端Chr 17上的一个位点， 与先前描述的Hst基因座的同源性。 这项建议有两个主要目标。 第一个目标是扩展基因 分析小鼠PAR，并开始对此进行物理分析 区域，利用先前工作已经产生的一些资源， 本建议书中所述的新资源。 物理 PAR的结构将与重组频率相关， 与发生在男性和女性中的重组位置有关， 雌性F1动物 第二，Ihtw 1将被精细映射， 将制作同源菌株以分离控制 最近分析的M.马其顿回交。 同源菌株表型的遗传分离是必要的 第一步是识别和克隆基因。 这一切成功都 基因至少有一个抑制基因，遗传实验被描述为 绘制影响杂种不育性的基因座的抑制基因图谱， 无论它们是显性还是隐性的。 发现的位点 近端Chr X及其抑制因子可能在引起 人类男性不育症。

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.