New insights into the physiological actions of selenoproteins from genetically modified mice

Abstract

SummarySelenium (Se) is an essential trace element in mammals. Dietary Se restriction or conditions of Se malabsorption lead to deficiency syndromes or exacerbate established diseases in humans and in many animal models. It is assumed that most, if not all, physiological actions of Se are mediated by selenocysteine (Sec) containing proteins. However, the exact role of particular selenoproteins for certain molecular pathways, for the metabolism of nutrients, hormones or cellular components and for the development and adaptive responses of the organism have often remained elusive. Through the use of transgenic animals, it becomes increasingly feasible to interfere specifically with the expression of single selenoproteins in certain tissues or at certain times. While some transgenic animals exhibit phenotypes that were expected from biochemical studies, in other instances the observed effects were a surprise in view of earlier hypotheses. IUBMB Life, 57: 737 -744, 2005

Comparative Analysis of Selenocysteine Machinery and Selenoproteome Gene Expression in Mouse Brain Identifies Neurons as Key Functional Sites of Selenium in Mammals

“…Of the six selenoproteins with elevated gene expression levels, the functions of SelM, SelW, Sep15, and SelK are not known. It is interesting, however, that classical gene targeting of SelP, but not liver-specific inactivation, leads to neurological dysfunction and motor incoordination (16,19,54). Although SelP-deficient mice can be rescued phenotypically by increasing dietary Se intake, synaptic function and spatial learning have been reported altered in the knockouts (57).…”

Selenium-Binding Protein 1 expression in ovaries and ovarian tumors in the laying hen, a spontaneous model of human ovarian cancer

“…Selenium is an essential micronutrient known for its role in the alleviation or prevention of inflammatory and autoimmune diseases, infertility, immunodeficiency diseases (HIV), thyroid function, cardiovascular disease and neurological diseases [1][2][3][4][5]. Because selenium inhibits cellular proliferation and promotes apoptosis of prostate, breast, endometrial, and lung cancer cells directly, it also plays a significant role in the reduction or prevention of multiple cancers [6][7][8].…”

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“…complicated picture of the physiologic functions of GPx (198,278). Mice deficient in the cellular GPx1 are healthy and fertile and show no increased oxidative stress or sensitivity to hyperoxia compared with wild-type mice.…”