DEVELOPMENTAL REGULATION OF FACTOR IX

我们建议：1)研究凝血因子IX的基因表达水平。 人类和小鼠的胎儿和新生儿作为我们的第一个模型 用于凝血因子的发育性表达，以及2) 发育基因调控机制的研究 构建含人因子转基因小鼠的表达 IX基因。 研究的第一条线将包括仔细分析 胎儿肝组织和小鼠肝组织中mRNA(浓度) 整个胎儿在非常早期的妊娠，在肝脏中 新生儿的组织。这些研究将为我们提供重要的 对人类水平和时间进程的认识也是如此 随着小鼠第IX因子基因在整个孕期和 新生儿期。这些结果将在 与报告的活性和抗原水平进行比较 这些组织中的因子IX，尤其是在人体组织中。 拟议研究项目的第二条线将包括 人凝血因子IX基因或其受体转基因小鼠的构建 为了详细研究Minigene的调控机制 这个基因。这项实验可能会让我们在 设计实验。利用这个系统，我们将进行测试和尝试 确定可能关键的dna序列(S)负责 因子IX基因的发育调控。 一旦我们能够获得关于因子IX的有希望的数据，我们就 计划将我们的类似工作扩展到其他凝血因子。

We propose: 1) to study levels of gene expression for factor IX in human as well as mouse fetuses and newborns as our first model for developmental expression of coagulation factors, and 2) to study the regulatory mechanism for developmental gene expression by constructing transgenic mice with the human factor IX gene. The first line of studies will include careful analysis of levels of the mRNA (concentration) in the liver tissues of fetuses or in the entire fetuses at very early gestational ages, and in the liver tissues of newborns. These studies will provide us important knowledge on the level and the time course of the human as well as mouse factor IX gene expression throughout gestation and neonatal period. These results will be carefully interpreted in comparison with the activity as well as antigen levels reported for factor IX in these tissues, particularly in the human tissue. The second line of proposed research project will include construction of transgenic mice with human factor IX gene or its minigene in order to study in detail the regulatory mechanism of this gene. This experiment may allow us much more flexibility in designing the experiments. Using this system, we will test and try to identify the possibly crucial DNA sequence(s) responsible for the developmental regulation of the gene for factor IX. Once we are able to obtain promising data on the factor IX we plan to extend our similar work to other coagulation factors.