The objective of the proposed research is to elucidate the molecular basis of the coordinated developmental expression of the pancreatic serine protease genes. The pancreatic serine protease genes are a family of homologous genes related by common evolution, function, and expression to high levels during pancreatic development. Recombinant DNA techniques have been and will be employed for the isolation of serine protease genes, the analysis of their sequence organization, and the identification of associated potential regulatory elements. We will exploit sequence comparisons between serine protease genes expressed in the pancreas and related serine protease genes expressed in other tissues to delineate sequences that may be involved in tissue-specific expression and to define the pattern of intron movement we have observed for this gene family. The experimental goals include: (1) To determine whether the pancreatic serine protease genes are clustered and whether clustering facilitates genetic mechanisms for their coordinated developmental regulation. (2) To determine whether the expression of one member of the serine protease family, kallikrein, in a large number of rat tissues involves single or multiple structural genes. (3) If a single kallikrein structural gene is expressed in more than one tissue, to investigate whether the regulatory mechanism may be discerned from the sequence organization. (4) To determine the functional importance of the position of intervening sequences and the evolution of changes in the number and position of intervening sequences within th serine protease genes. (5) To develop an in vivo assay to identify gene regulatory regions required for pancreas-specific expression.
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