THE HUMAN LYSOZYME PROMOTER DIRECTS REPORTER GENE-EXPRESSION TO ACTIVATED MYELOMONOCYTIC CELLS IN TRANSGENIC MICE

The 5' region of the human lysozyme gene from -3500 to +25 was fused t o a chloramphenicol acetyltransferase (CAT) reporter gene and three tr ansgenic founder mice were obtained. All three transgenic lines showed the same pattern of CAT enzyme expression in adult mouse tissues that was consistent with the targeting of elicited, activated macrophages in tissues and developing and elicited granulocytes. In normal mice hi gh CAT enzyme activity was found in the spleen, lung, and thymus, tiss ues rich in phagocytically active cells, but not in many other tissues , such as the gut and muscle, which contain resident macrophages. Cult ured resident peritoneal macrophages and cells elicited 18 hr (granulo cytes) and 4 days (macrophages) after injection of sterile thioglycoll ate broth expressed CAT activity. Bacillus Calmette-Guerin infection o f transgenic mice resulted in CAT enzyme expression in the liver, whic h contained macrophage-rich granulomas, whereas the liver of uninfecte d mice did not have any detectable CAT enzyme activity, Although the P aneth cells of the small intestine in both human and mouse produce lys ozyme, the CAT gene, under the control of the human lysozyme promoter, was not expressed in the mouse small intestine. These results indicat e that the human lysozyme promoter region may be used to direct expres sion of genes to activated mouse myeloid cells.