DEVELOPMENTAL GENETICS OF MOUSE CHROMOSOME 2

描述（改编自研究者的摘要）：申请人建议 识别调节早期哺乳动物发育的基因。进展情况 由于对后来发展的机制的理解很快 从果蝇到小鼠的基因功能的保守。然而，基因靶向 小鼠直系同源物关于早期事件的信息要少得多 卵裂、压实、胚外组织的发生、植入、 轴测定、原肠胚形成和神经诱导。新策略是 必要的。一种直接的遗传方法来识别和表征早期 提出了发育基因。首先，小鼠2号染色体的缺失 将被生成。这些缺失将在胚胎干 (ES) 细胞中产生 将在其中映射它们并克隆断点。缺失染色体 将在小鼠中建立。其次，早期发育表型 以我们所做的删除以及现有的删除为特征 2号染色体。重叠和嵌套缺失将用于绘制基因图谱，这 对于从分裂到神经诱导的早期发育是必需的。最后， 将构建平衡染色体 2。平衡染色体将 允许有效筛选化学诱导的基因点突变 用缺失染色体定义。

DESCRIPTION (Adapted from investigator's abstract): The applicant proposes to identify genes regulating early mammalian development. Progress in understanding mechanisms of later development has been rapid due to the conservation of gene function from Drosophila to mouse. However, gene targeting of mouse orthologues has been much less informative about the early events of cleavage, compaction, genesis of the extra-embryonic tissues, implantation, axis determination, gastrulation and neural induction. New strategies are necessary. A direct, genetic approach to identifying and characterizing early developmental genes is proposed. Firstly, deletions covering mouse chromosome 2 will be generated. These deletions will be created in embryonic stem (ES) cells where they will be mapped and the breakpoints cloned. The deletion chromosomes will be established in mice. Secondly, early developmental phenotypes will be characterized for the deletions we make, and for existing deletions of chromosome 2. Overlapping and nested deletions will be used to map genes, which are necessary for early development, from cleavage to neural induction. Lastly, a balancer chromosome 2 will be constructed. The balancer chromosome will permit efficient screening for chemically induced point mutations in the genes defined with the deletion chromosomes.