Mouse models for Glutathione Peroxidase 4 (GPx4).

The selenoperoxidase glutathione peroxidase 4 (GPx4 – also frequently referred to as phospholipid hydroperoxide glutathione peroxidase, PHGPx) is one of the eight glutathione peroxidases in mammals, but the only one known to be essential for early mouse development. GPx4 is emerging as one of the most central selenoproteins, and thus has attracted considerable interest in recent years. Key insights into GPx4 function came from the numerous transgenic and knockout mouse studies performed mainly during the last couple of years, which are summarized here. These investigations not only firmly established a crucial role for GPx4 in male fertility and neuroprotection, but also indicated a major regulatory role of GPx4 in oxidative stress-induced cell death signaling. Beyond this, lipid hydroperoxides (LOOH), downstream of GPx4 inactivation, have been recently shown to control receptor tyrosine kinase (RTK) signaling, thus adding a new layer of complexity to the multifaceted roles of GPx4 in cell signaling and disease development