THE MYELOPEROXIDASE GENE PROXIMAL ENHANCER DIRECTS HEMATOPOIETIC-SPECIFIC EXPRESSION IN TRANSGENIC MICE

The myeloperoxidase (MPO) gene is expressed specifically in immature m yeloid cells. The MPO gene includes a promoter proximal enhancer which is coincident with DNaseI hypersensitive chromatin sites and is speci fically active in myeloid cell lines. We developed transgenic murine l ines in which 1.3 kb of murine MPO proximal 5' flanking region DNA was linked to a TATAA homology and RNA initiation site derived from the H SV-TK promoter and to a luciferase reporter (MPOTKLUC). In each of six founder lines, high-level luciferase activity was evident in marrow, thymus and spleen. Modest-to high-level luciferase expression was also evident in brain and in the heart in several of the lines, and lucife rase activity was at or near background levels in lung, liver, kidney, stomach, colon, bladder, skeletal muscle, skin and small intestine in all of the MPOTKLUC transgenic mice. Within marrow cells, luciferase activity was evident in myeloid (GR-1+), B lymphoid (B220+) and T-lymp hoid (CD4+) cells. Additional regulatory regions, thus, may be require d to further restrict MPO gene expression to immature myeloid cells. ( C) 1997 Elsevier Science B.V.