DEVELOPMENTAL GENETICS OF MOUSE CHROMOSOME 2

小鼠 2 号染色体的发育遗传学

• 批准号: 6128268
• 负责人: RONALD A. CONLON
• 金额: $ 27.54万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6128268
• 关键词: cell line; chromosomes; developmental genetics; electroporation; embryonic stem cell; fluorescent in situ hybridization; gene deletion mutation; gene expression; gene targeting; genetic mapping; genetic markers; genetic recombination; karyotype; laboratory mouse; mammalian embryology; molecular cloning; phenotype; polymerase chain reaction; regulatory gene; southern blotting

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.

描述（根据调查员的摘要改编）：申请人建议 确定调节早期哺乳动物发育的基因。进步 由于理解后来发展的机制一直很快 从果蝇到小鼠的基因功能保存。但是，基因靶向 鼠标直系同源的人对早期事件的信息不足 裂解，压实，胚外组织的起源，植入， 轴确定，胃诱导和神经诱导。新策略是 必要的。一种直接的遗传方法来识别和表征早期的表征 提出了发展基因。首先，覆盖鼠标2的缺失2 将生成。这些缺失将在胚胎茎（ES）细胞中产生 它们将在哪里映射，并克隆断点。缺失染色体 将在老鼠中建立。其次，早期的发育表型将是 为我们所做的删除和现有删除的特征 染色体2。重叠和嵌套缺失将用于绘制基因，这些基因 从乳沟到神经诱导是早期发展所必需的。最后， 将构建平衡器2的平衡器染色体。平衡器染色体将 允许对基因化学诱导点突变进行有效筛选 用缺失染色体定义。