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Targeted removal of the selenocysteine tRNA [Ser]Sec gene ( trsp ) in mouse macrophages
Author(s) -
Carlson Bradley A,
Shrimali Rajeev K,
Irons Robert,
Park Jin Mo,
Hatfield Dolph L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a717-d
Subject(s) - selenocysteine , immune system , knockout mouse , gene knockout , cre recombinase , biology , lipopolysaccharide , gene , conditional gene knockout , chemokine , microbiology and biotechnology , phenotype , immunology , genetics , transgene , biochemistry , genetically modified mouse , enzyme , cysteine
Selenium is essential for proper immune function and protection of the immune system from oxidative damage, though the role of different forms of selenium (i.e., low molecular weight selenocompounds or selenoproteins [SPs]) in this process is not known. Herein, we have specifically removed the expression of SPs in macrophages of mice using Cre/ loxP technology by crossing a mouse containing a floxed selenocysteine (Sec) tRNA gene with a mouse expressing the Cre‐ recombinase gene under the control of the M lysozyme (LysM) promoter thereby specifically removing Sec tRNA expression and, thus, SPs, in this cell type. The resulting knockout mice manifest no apparent phenotype in the absence of an immune challenge. Studies are currently underway to investigate the activation of pro‐inflammatory signaling pathways as well as the production of cytokines, chemokines and other inflammatory mediators in both wild type and knockout macrophages upon stimulation with lipopolysaccharide in vitro . Future studies will investigate the susceptibility of knockout mice to bacterial infection and sepsis and will examine the role of SPs in experimentally‐induced inflammatory diseases. This model will help to identify the critical role of SPs and/or low molecular weight selenocompounds in immune system regulation. This research was supported by the Intramural Research Program of the NIH, NCI, CCR.