DEVELOPMENTAL REGULATION OF FACTOR IX

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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.