Bibliographic Citation
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| Title | Transgenic control of perforin gene expression |
| Creator/Author | Lichtenheld, M.G. ; Podack, E.R. ; Levy, R.B. [Univ. of Miami, FL (United States)] |
| Publication Date | 1995 Mar 01 |
| OSTI Identifier | OSTI ID: 75584 |
| Other Number(s) | Journal ID: JOIMA3; ISSN 0022-1767; TRN: TRN: 95:004233-0001 |
| Resource Type | Journal Article |
| Resource Relation | Journal Name: Journal of Immunology; Journal Volume: 154; Journal Issue: 5; Other Information: PBD: 1 Mar 1995 |
| Subject | 55 BIOLOGY AND MEDICINE, BASIC STUDIES; TRANSCRIPTION; CONTROL; GENES; DNA HYBRIDIZATION; NATURAL KILLER CELLS; CHEMICAL ACTIVATION; GENE REGULATION; TRANSGENIC MICE; MESSENGER-RNA; LYMPHOCYTES |
| Description/Abstract | Perforin is a pore-forming effector molecule of CTL and NK cells. To characterize perforin gene expression and its transcriptional control mechanisms in vivo, expression of a cell surface tag, i.e., human CD4, was driven by 5.1 kb of the murin perforin 5{prime} flanking and promoter region in transgenic mice. Six out of seven transgenic lines expressed the perforin-tag hybrid gene at low to intermediate levels, depending on the integration site. Transgene expression occurred in all cells that physiologically are able to express perforin. At the whole organ level, significant amounts of transgenic mRNA and endogenous perforin mRNA were co-expressed in the lymphoid organs, as well as in the lung, the ileum, the oviduct/uterus, and the bone marrow. At the single cell level, the perforin tag was present on NK cells and on CD8{sup +}, as well as on CD4{sup +} cells. Also targeted were Thy-1.2{sup +} {gamma}{delta} T cells, but not Thy-1.2{sup -} {gamma}{delta} T cells, B cells, nor monocytes. During thymic T cell development, transgene expression occurred in double negative (CD4{sup -}CD8{sup -}) thymocytes and was detected at all subsequent stages, but exceeded the expression levels of the endogenous gene in the thymus. In conclusion, the analyzed perforin 5{prime} flanking and promoter region contains important cis-acting sequences that restrict perforin expression to T cells and NK cells, and therefore provides a unique tool for manipulating T cell and/or Nk cell-mediated immune responses in transgenic mice. On the other hand, the normal control of perforin gene expression involves at least one additional negative control mechanism that was not mediated by the transgenic promoter and upstream region. This control restricts perforin gene expression in thymically developing T cells and in most resting peripheral T cells, but can be released upon T cell activation. 43 refs., 7 figs., 1 tab. |
| Country of Publication | United States |
| Language | English |
| Format | Medium: X; Size: pp. 2153-5163 |
| System Entry Date | 2009 Dec 16 |
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