ANALYSIS AND CLONING OF THE MOUSE EXED GENE

虽然胎盘发育或功能的失败是 人类妊娠期胚胎死亡的最常见原因 和其他脊椎动物一样，人们对其基因调控知之甚少 胚胎外发育。中确定的一个功能单元 7号染色体上的白化缺失复合体，它在 小鼠早期植入后为胚外外胚层 发展(前)地区。用于缺失的纯合子胚胎 移除这一区域显示胚胎外的异常 结构，特别是在胚胎外胚层中，这是 严重萎缩和固缩。这些胚胎的发育是 被截断后，它们在胚胎7.5-8.0天左右死亡。这是未知的 主要的影响是否在胚胎外发育，因为 胚胎外胚层也很小。EXED的角色将是 通过挽救胚胎外部分或胚胎部分来阐明 具有四倍体-二倍体嵌合体的表型。删除 互补分析表明，丢失了20kb 地区是表型所必需的。然而，目前还不清楚 该区域在缺失时是否足以引起表型， 或者是否在20kb区外移除的其他基因也 对外在表型有贡献。为了澄清这个问题，20 kb 将使用CRE-loxP系统删除目标区域 同源重组。最后，将对exed进行定位克隆， 搜索从20kb区域开始。

Although failure of placental development or function is one of the most common causes of embryonic death during gestation in humans and other vertebrates, little is known about the genetic regulation of extraembryonic development. One functional unit identified in the albino-deletion complex on chromosome 7 which is important during early postimplantation in the mouse is the extraembryonic ectoderm development (exed) region. Embryos homozygous for deletions removing this region display abnormalities of extraembryonic structures, particularly in the extraembryonic ectoderm which is severely reduced and pyknotic. Development of these embryos is truncated and they die around embryonic day 7.5-8.0. It is unknown whether the primary effect is on extraembryonic development since the embryonic ectoderm is also small. The role of exed will be clarified by rescuing either the extraembryonic or embryonic portion of the phenotype with tetraploid-diploid chimeras. Deletion complementation analyses have demonstrated that loss of a 20 kb regiori is necessary for the phenotype. However it is not known whether this region is sufficient to cause the phenotype when deleted, or whether other genes removed outside the 20 kb region also contribute to the exed phenotype. To clarify this issue, the 20 kb region will be deleted using the Cre-loxP system with targeted homologous recombination. Finally, exed will be positionally cloned, with the search beginning in the 20 kb region.