TARGETING GENE-EXPRESSION TO ENDOTHELIAL-CELLS IN TRANSGENIC MICE USING THE HUMAN INTERCELLULAR-ADHESION MOLECULE-2 PROMOTER

Genetic engineering of donor animals in xenotransplantation research h as been directed largely toward obtaining expression of various immuno regulatory molecules on vascular endothelium, the initial target of re cipient antibody and complement, However, specific high-level expressi on of transgenes throughout the vascular tree in adult animals has pro ved difficult to achieve, perhaps because of the inherent heterogeneit y of endothelium, Using the promoter of the gene for intercellular adh esion molecule 2 (ICAM-2), which is constitutively expressed on all va scular endothelium, we have developed a system for endothelial cell ge ne targeting in vivo. A 334-basepair fragment from the 5' flanking reg ion of the human ICAM-2 gene was used to drive the expression of human CD59 in transgenic mice. Strong and uniform expression of CD59 was ob served on the endothelial cells of all blood vessels in the heart, kid ney, lung, liver, and pancreas in the three lines of mice examined. Li ttle or no expression was seen in other cell types, with the exception of neutrophils and monocytes, These results suggest that this small p romoter region contains most of the signals necessary to endow it with endothelial cell specificity, making it a potentially valuable tool i n areas ranging from xenotransplantation to gene therapy.