Hepatically derived selenoprotein P is a key factor for kidney but not for brain selenium supply

Liver-specific inactivation of Trsp, the gene for selenocysteine tRNA, removes SePP (selenoprotein P) from plasma, causing serum selenium levels to fall from 298 mu g/l to 50 mu g/l and kidney selenium to decrease to 36 % of wild-type levels. Likewise, glutathione peroxidase activities decreased in plasma and kidney to 43 % and 18 % respectively of wild-type levels. This agrees nicely with data from SePP knockout mice, supporting a selenium transport role for hepatically expressed SePP. However, brain selenium levels remain unaffected and neurological defects do not occur in the liver-specific Trsp knockout mice, while SePP knockout mice suffer from neurological defects. This indicates that a transport function in plasma is exerted by hepatically derived SePP, while in brain SePP fulfils a second, hitherto unexpected, essential role.