Specific expression of an elastase–human growth hormone fusion gene in pancreatic acinar cells of transgenic mice

Abstract

Transfection of genes into tissue culture cell lines has demonstrated that relatively short DNA sequences can allow expression of inmiunoglobulin^1–3, insulin and chymotrypsin⁴ genes in their appropriate cell types. A definitive test of cell-specific gene expression, however, requires testing genes in every possible cell type, an experiment performed easily by introducing the gene in question into the germ line of an animal. Transfer of intact genes into mice has demonstrated that a mouse immunglobulin κ gene is expressed specifically in B lymphocytes^5,6, a rat elastase I gene is expressed specifically in pancreas⁷ and a chicken transferrin gene is expressed preferentially in liver⁸. Mouse metallothionein-growth hormone fusion genes introduced into mice are preferentially expressed in the liver, consistent with the expression of endogenous metallothionein genes⁹, but initial experiments with β-globin genes have not revealed proper regulation^10–12. To identify the DNA elements required for pancreas-specific expression of the rat elastase I gene, we joined the 5′-flanking region of this gene to the human growth hormone (hGH) structural gene and introduced the fusion gene into mice. Here we demonstrate that a fusion gene containing only 213 base pairs (bp) of elastase I gene sequence directs expression of hGH in pancreatic acinar cells.