DEVELOPMENTAL GENETICS OF MOUSE CHROMOSOME 2

描述(改编自调查人员摘要)：申请人建议 识别调控哺乳动物早期发育的基因。取得的进展 对后来发展的机制的理解之所以迅速，是因为 从果蝇到小鼠的基因功能保守性。然而，基因打靶 对早期事件的信息量要小得多 卵裂，压实，胚胎外组织的发生，植入， 轴测定、原肠形成和神经诱导。新的战略是 这是必要的。一种直接的、遗传的方法来识别和表征早期 提出了发育基因的概念。首先，覆盖小鼠2号染色体的缺失 将会被生成。这些缺失将在胚胎干细胞中产生 它们将在哪里映射并克隆断点。缺失的染色体 将在小鼠身上建立。其次，早期发育表型将是 特点是我们所做的删除，以及现有的删除 染色体2.重叠和嵌套缺失将被用来定位基因，这 是从卵裂到神经诱导的早期发育所必需的。最后， 将构建一个平衡器2号染色体。平衡器染色体将会 允许对化学诱导的基因点突变进行有效筛选 定义为缺失的染色体。

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.