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Knockout of the selenocysteine tRNA [Ser]Sec gene ( Trsp ) in mouse macrophages
Author(s) -
Carlson Bradley A,
Yoo MinHyuk,
Kim Jin Young,
Shrimali Rajeev K,
Irons Robert,
Park Jin Mo,
Hatfield Dolph L
Publication year - 2009
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.23.1_supplement.346.7
Subject(s) - selenocysteine , selenoprotein , knockout mouse , immune system , gene knockout , biology , gene , gene expression , microbiology and biotechnology , oxidative stress , genetics , superoxide dismutase , biochemistry , glutathione peroxidase , enzyme , cysteine
Selenium has been shown to play a role in proper immune function and protection of the immune system from oxidative damage, though the form of selenium (i.e., low molecular weight selenocompounds and/or selenoproteins) utilized in this process is not clear. In this study, we have specifically removed the expression of selenoproteins in macrophages of mice by crossing a mouse containing a floxed selenocysteine (Sec) tRNA gene with a mouse expressing the Cre‐recombinase gene under the control of the lysozyme M (LysM) promoter. The selenoprotein knockout mice have no apparent phenotype in the absence of an immune challenge. However, removal of selenoproteins in macrophages showed an accumulation of reactive oxygen species (ROS) levels in knockout bone marrow‐derived macrophages compared to wild type controls. Knockout macrophages also exhibit impaired invasiveness using an in vitro matrigel assay. Correspondingly, microarray analysis has identified altered expression of several extracellular matrix and fibrosis‐associated genes and these results have been verified by qPCR analysis. The altered gene expression does not appear to be a result of increased ROS levels, as treatment with NAC had little effect on altered gene expression. These findings suggest that selenoproteins exert immune regulatory functions at multiple levels. This research was supported by the Intramural Research Program of the NIH, NCI, CCR.