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Showing papers by "Raymond J. MacDonald published in 1986"


Journal ArticleDOI
TL;DR: This work has chosen to study the expression of a family of pancreas-specific genes-the pancreatic serine proteases-because of the advantages that accrue from the comparative analysis of similarly regulated genes.
Abstract: The differential expression of genes that determine cellular phenotype is largely regulated by controlling the rate of initiation of transcription of these genes. To understand this aspect of cell differentiation it is necessary to define the genetic and molecular mechanisms that determine the timing, the extent, and the tissue-specific nature of transcription of developmentally regulated genes. We have chosen to study the expression of a family of pancreas-specific genes-the pancreatic serine proteases-because of the advantages that accrue from the comparative analysis of similarly regulated genes. At least nine distinct serine protease genes (three chymotrypsin genes, three trypsin genes, two elastase genes, and one kallikrein gene) are expressed in the exocrine pancreas of the rat. The gene family has evolved from a common ancestral serine protease gene through a series of duplications.' The family members encode enzymes that are structurally and functionally homologous. Each gene is expressed to high levels and selectively in the acinar cells of the pancreas as part of the differentiative phenotype of this cell type. With the exception of kallikrein: the presence of enzymes with similar activities in other tissues appears due to expression of the protein products of related but distinct genes. Moreover, expression in the acinar cells of the pancreas is very high: about 20% of the total protein synthesis of the gland is for these few serine proteases.'

17 citations


Journal ArticleDOI
01 Oct 1986
TL;DR: The stable inheritance of expression of the foreign rat elastase I genes in transgenic mice allows the development of animal lines that synthesize and secrete high levels of foreign protein by the pancreas.
Abstract: Six different lines of transgenic mice bearing rat elastase I genes stably inherit both the high-level pancreatic expression and low-level nonpancreatic expression characteristic of each o...

15 citations


Journal ArticleDOI
TL;DR: Predictive methods have been extended to generate a proposed tertiary structure of rat elastase II on the basis of primary amino acid sequence and structural homologies within the family of mammalian serine proteinases that suggests probable substrate cleavage preferences.

10 citations