Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses.
Verma S, Hoffmann FW, Kumar M, Huang Z, Roe K, Nguyen-Wu E, Hashimoto AS, Hoffmann PR.
Verma S, Hoffmann FW, Kumar M, Huang Z, Roe K, Nguyen-Wu E, Hashimoto AS, Hoffmann PR. (2011) Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses. Journal of Immunology 186(4):2127-2137.
Selenoprotein K (Sel K) is a selenium-containing protein for which no function has been identified. We found that Sel K is an endoplasmic reticulum transmembrane protein expressed at relatively high levels in immune cells and is regulated by dietary selenium. Sel K(-/-) mice were generated and found to be similar to wild-type controls regarding growth and fertility. Immune system development was not affected by Sel K deletion, but specific immune cell defects were found in Sel K(-/-) mice. Receptor-mediated Ca(2+) flux was decreased in T cells, neutrophils, and macrophages from Sel K(-/-) mice compared with controls. Ca(2+)-dependent functions including T cell proliferation, T cell and neutrophil migration, and Fc? receptor-mediated oxidative burst in macrophages were decreased in cells from Sel K(-/-) mice compared with that in cells from controls. West Nile virus infections were performed, and Sel K(-/-) mice exhibited decreased viral clearance in the periphery and increased viral titers in brain. Furthermore, West Nile virus-infected Sel K(-/-) mice demonstrated significantly lower survival (2 of 23; 8.7%) compared with that of wild-type controls (10 of 26; 38.5%). These results establish Sel K as an endoplasmic reticulum-membrane protein important for promoting effective Ca(2+) flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses.