DEVELOPMENTAL GENETICS OF MOUSE CHROMOSOME 2

描述（改编自研究者摘要）：申请人建议 鉴定调节哺乳动物早期发育的基因。进展 对后来发展机制的理解很快， 从果蝇到小鼠的基因功能保守性。然而，基因靶向 小鼠直系同源物的研究对早期的 卵裂、致密化、胚外组织的发生、植入、 轴决定、原肠胚形成和神经诱导。新的战略 必要一种直接的遗传学方法来识别和表征早期 发育基因的提出。首先，覆盖小鼠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 在那里它们将被映射并克隆断点。缺失染色体 将在小鼠中建立。其次，早期发育表型将是 我们所做的删除，以及现有的删除， 2号染色体。重叠和巢式缺失将用于绘制基因， 是早期发育所必需的，从卵裂到神经诱导。最后， 将构建平衡染色体2。平衡染色体将 允许有效筛选基因中化学诱导的点突变， 用缺失染色体来定义。

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.