ANALYSIS OF HUMAN CD59 TISSUE EXPRESSION DIRECTED BY THE CMV-IE-1 PROMOTER IN TRANSGENIC RATS

The investigation of human complement (C) inhibitors with a view to ov ercoming C-mediated tissue injury stands to benefit from the productio n of anatomically suitable transgenic animals. Ln this study, we used the CMV-IE1 enhancer/promoter to control the expression in vivo in tra nsgenic rats of the human terminal C protein inhibitor CD59. Five tran sgenic rats were identified, of which four possessed at least one comp lete copy of the transgene. The presence of human CD59 transcripts and protein was demonstrated in two transgenic rat lines. A widespread ti ssue distribution of cells expressing human CD59, similar in the two l ines, was observed-principally in pancreas, brain, heart, kidney, inte stine and striated muscle. Whereas expression in pancreas and brain wa s uniform, mosaicism of CD59 expression was observed in some tissues s uch as heart and kidney, a proportion of cells within the tissue not e xpressing the transgene. Immunohistological analysis revealed surface expression of human CD59 in a variety of cells, including fibroblasts, epithelial cells and muscle cells, but not in endothelial cells. In c onclusion, this paper analyses at the cellular level human CD59 expres sion directed by the CMV promoter in transgenic rats, and discusses ho w they could be used to investigate in vivo the role of C in a variety of pathologies.