Insights from Selenoprotein I mouse models for understanding biological roles of this enzyme.

Abstract

Selenoprotein I (selenoi) is a metabolic enzyme expressed in a wide variety of tissues that catalyzes the transfer of the ethanolamine phosphate group from CDP-ethanolamine to lipid acceptors to generate ethanolamine phospholipids. It is a member of the selenoprotein family, a class of proteins that mostly play fundamental roles in redox homeostasis and are defined by the co-translational incorporation of selenium in the form of selenocysteine. Loss-of-function mutations in the human SELENOI gene have been found in rare cases leading to a complex form of hereditary spastic paraplegia. Understanding the roles of this selenoprotein and its phospholipid products in different cell types has benefited from the development of mouse models. In particular, global and conditional knockout (KO) of the Selenoi gene in mice has enabled a more complete picture to emerge of how this important selenoprotein is integrated into metabolic pathways. These data have revealed how Selenoi loss-of-function affects embryogenesis, neurodevelopment, the immune system and liver physiology. This review summarizes the insights gained through mouse model experiments and the current understanding the different physiological roles played by this selenoprotein.