Deletion of selenoprotein P gene in the mouse

Abstract

Selenoprotein P is a selenium-rich extracellular protein that has a number of unusual characteristics. The recent production of mice with selenoprotein P deleted (Seppl -/- mice) has fostered studies of its function. Selenoprotein P has been shown to have a role in whole-body selenium homeostasis. When fed diets containing selenium at its required concentration, Seppl -/- mice have lower tissue selenium concentrations than do Seppl +/+ mice, except in the liver. Thus, selenoprotein P appears to distribute selenium from the liver to other tissues. Also, Seppl -/- mice develop neurological dysfunction and have male infertility. Both brain and testis in them have very low selenium concentrations and appear to be selenium deficient. Feeding Seppl -/- mice high dietary levels of selenium prevents most of the neurological dysfunction but does not raise brain selenium concentration or prevent brainstem axonal degeneration. Thus, the functions of selenoprotein P in the central nervous system appear to be complex and are not explained by a single mechanism. Spermatozoa produced by Seppl -/- mice are morphologically similar to those of selenium deficient Seppl +/+ mice. They lack a mitochondrial sheath covering the distal midpiece. Absence of the sheath causes axonemal disruption that leads to a hairpin bend at the midpiece-principal piece junction. The resulting spermatozoa have markedly reduced motility, presumably a cause of their ineffectiveness.These findings suggest that the primary function of selenoprotein P in the testis is to provide selenium to be used in sperm production.