Mammalian Developmental Genetics And Animal Models Of Hu

哺乳动物发育遗传学和胡动物模型

• 批准号: 7333370
• 负责人: HEINER WESTPHAL
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7333370
• 关键词: Mammalian; Developmental; Genetics; Animal; Models

We study the molecular genetics of mammalian development. Our interest is focused on developmental controls exerted by LIM-homeodomain (LIM-HD) transcription factors that are encoded by individual members of the Lhx gene family. In the embryo, and also in the adult, Lhx Genes mediate the transit from the stem cell stage to a precursor stage that precedes terminal differentiation. In our earlier experiments, we determined the functions of a number of Lhx genes through loss-of-function analysis of knockout mice, and we described obligatory cofactors, encoded by Ldb and Ssdp genes, respectively, that mediate Lhx gene function. In the work described here, we have adopted regimens of Cre-mediated conditional mutation, originally developed in our laboratory, to ask more fine-tuned questions regarding the action of LIM-HD/cofactor complexes and their downstream Dkk targets as patterns form and organs are established in the developing mouse embryo.

我们研究哺乳动物发育的分子遗传学。我们的兴趣集中在LIM同源结构域(LIM-HD)转录因子施加的发育控制上，LIM-HD是由LHX基因家族的单个成员编码的。在胚胎中，以及在成体中，lhx基因介导从干细胞阶段到终末分化之前的前体阶段的过渡。在我们早期的实验中，我们通过对敲除小鼠的功能丧失分析来确定一些lhx基因的功能，并描述了分别由LDB和SSDP基因编码的介导lhx基因功能的强制性辅因子。在这里描述的工作中，我们采用了最初由我们实验室开发的Cre介导的条件突变方案，以提出关于LIM-HD/辅因子复合体及其下游DKK靶点的更微调的问题，因为模式形式和器官在发育中的小鼠胚胎中建立。