The human lysozyme promoter directs reporter gene expression to activated myelomonocytic cells in transgenic mice.

Abstract

The 5' region of the human lysozyme gene from -3500 to +25 was fused to a chloramphenicol acetyltransferase (CAT) reporter gene and three transgenic 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 high CAT enzyme activity was found in the spleen, lung, and thymus, tissues rich in phagocytically active cells, but not in many other tissues, such as the gut and muscle, which contain resident macrophages. Cultured resident peritoneal macrophages and cells elicited 18 hr (granulocytes) and 4 days (macrophages) after injection of sterile thioglycollate broth expressed CAT activity. Bacillus Calmette-Guérin infection of transgenic mice resulted in CAT enzyme expression in the liver, which contained macrophage-rich granulomas, whereas the liver of uninfected mice did not have any detectable CAT enzyme activity. Although the Paneth cells of the small intestine in both human and mouse produce lysozyme, the CAT gene, under the control of the human lysozyme promoter, was not expressed in the mouse small intestine. These results indicate that the human lysozyme promoter region may be used to direct expression of genes to activated mouse myeloid cells.

Conserved and Tissue-Specific Genic and Physiologic Responses to Caloric Restriction and Altered IGFI Signaling in Mitotic and Postmitotic Tissues

“…The downregulation of four inflammation-related genes in LTCR liver and heart is consistent with the reduced inflammation often reported for LTCR mice (15 ; Table 1). For example, Lyzs (lysozyme) is an inducible marker of macrophage activation and inflammatory disease (16,64). IL13R (interleukin 13 receptor) is overexpressed in human tumor cells (116), and IL-13 is a major inducer of fibrosis through induction of transforming growth factor β1 in macrophages (34).…”

Macrophage Deletion of p38α Partially Impairs Lipopolysaccharide-Induced Cellular Activation

“…Because of restricted cell type expression of Cre by the lysozyme promoter (32,33), the floxed p38␣ gene was detected in adult tissues of both p38␣ fl/fl and LtrLys Cre -p38␣ ⌬/⌬ mice, despite of the presence of transgene cre in the tissues of LtrLys Cre -p38␣ ⌬/⌬ mice (Fig. 1B, left).…”

Autocrine Deactivation of Macrophages in Transgenic Mice Constitutively Overexpressing IL-10 Under Control of the Human CD68 Promoter

“…For these reasons, we were interested in creating a mouse model to analyze the consequences of overexpression of IL-10 from macrophages themselves. To direct transgene expression to macrophages, promoter fragments of the CD11b (20), c-fms (21), scavenger receptor A (SR-A) (22), lysozyme (23), and MHC class II (MHC-II) (24) genes have been used. None of these constructs is ideal for macrophage-specific expression of transgenes, because they are either not restricted to macrophages or only active in a subset of these cells.…”