DEVELOPMENTAL REGULATION OF FACTOR IX

我们建议：1）研究基因表达水平的因子IX， 人类以及小鼠胎儿和新生儿作为我们第一个模型 用于凝血因子的发育表达，和2） 研究发育基因的调控机制 构建人因子转基因小鼠表达 IX基因。 研究的第一线将包括仔细分析 胎儿肝组织或 整个胎儿在非常早期的胎龄，并在肝脏 新生儿的组织。 这些研究将为我们提供重要的 对人的层次和时间进程的认识， 小鼠凝血因子IX基因在整个妊娠期的表达， 新生儿期 这些结果将被仔细解释， 与报告的活性以及抗原水平相比， 在这些组织中，特别是在人体组织中， 建议研究项目的第二行将包括 人凝血因子IX基因或其转基因小鼠的构建 小基因，以详细研究调控机制， 这个基因。 这个实验可能会让我们有更多的灵活性， 设计实验。 利用这个系统，我们将测试和尝试 以确定可能的关键DNA序列， 第九因子基因的发育调控 一旦我们能够获得关于因子IX的有希望的数据， 计划将我们类似的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.