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Publication : Early myeloid cell-specific expression of the human cathepsin G gene in transgenic mice.

First Author  Grisolano JL Year  1994
Journal  Proc Natl Acad Sci U S A Volume  91
Issue  19 Pages  8989-93
PubMed ID  8090757 Mgi Jnum  J:47502
Mgi Id  MGI:1203649 Doi  10.1073/pnas.91.19.8989
Citation  Grisolano JL, et al. (1994) Early myeloid cell-specific expression of the human cathepsin G gene in transgenic mice. Proc Natl Acad Sci U S A 91(19):8989-93
abstractText  The human cathepsin G (CG) gene is expressed only in promyelocytes and encodes a neutral serine protease that is packaged in the azurophil (primary) granules of myeloid cells. To define the cis-acting DNA elements that are responsible for promyelocyte-specific targeting, we injected a 6-kb transgene containing the entire human CG gene, including coding sequences contained in a 2.7-kb region, approximately 2.5 kb of 5' flanking sequence, and approximately 0.8 kb of 3' flanking sequence. Seven of seven transient transgenic murine embryos revealed human CG expression in the fetal livers at embryonic day 15. Stable transgenic founder lines were created with the same 6-kb fragment; four of five founder lines expressed human CG in the bone marrow. The level of human CG expression was relatively low per gene copy when compared with the endogenous murine CG gene, and expression was integration-site dependent; however, the level of gene expression correlated roughly with gene copy number. The human CG transgene and the endogenous murine CG gene were coordinately expressed in the bone marrow and the spleen. Immunohistochemical analysis of transgenic bone marrow revealed that the human CG protein was expressed exclusively in myeloid cells. Expression of human CG protein was highest in myeloid precursors and declined in mature myeloid cells. These data suggest that the human CG gene was appropriately targeted and developmentally regulated, demonstrating that the cis-acting DNA sequences required for the early myeloid cell-specific expression of human CG are present in this small genomic fragment.
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