Glutathione peroxidase (Gpx1) is the major selenoprotein in most tissues in 
animals. Knockout (KO) of Gpx1 decreases Gpx1 activity to near zero and 
substantially reduces liver selenium (Se) levels, but has no overt effects in 
otherwise healthy mice. To investigate the impact of deletion of Gpx1 on Se 
metabolism, Se flux, and apparent Se requirements, KO, Gpx1 heterozygous (Het), 
and Gpx1 wild-type (WT) mice were fed Se-deficient diet for 17 weeks, then 
repleted with graded levels of Se (0-0.3 μg Se/g as Na2SeO3) for 7 days, and 
selenoprotein activities and transcripts were determined in blood, liver, and 
kidney. Se deficiency decreased the activities of plasma Gpx3, liver Gpx1, liver 
Txnrd, and liver Gpx4 to 3, 0.3, 11, and 50% of WT Se-adequate levels, 
respectively, but the Gpx1 genotype had no effect on growth or changes in 
activity or expression of selenoproteins other than Gpx1. Se repletion increased 
selenoprotein transcripts to Se-adequate levels after 7 days; Se response curves 
and apparent Se requirements for selenoprotein transcripts were similar to those 
observed in studies starting with Se-adequate mice. With short-term Se 
repletion, selenoenzyme activities resulted in three Se response curve patterns: 
(1) liver and kidney Gpx1, Gpx4, and Txnrd activities were sigmoidal or 
hyperbolic with breakpoints (0.08-0.19 μg Se/g) that were double those observed 
in studies starting with Se-adequate mice; (2) red blood cell Gpx1 activity was 
not significantly changed; and (3) plasma Gpx3 activity only increased 
substantially with 0.3 μg Se/g. Plasma Gpx3 is secreted from kidney. In this 
short-term study, kidney Gpx3 mRNA reached plateau levels at 0.1 μg Se/g, and 
other kidney selenoenzyme activities reached plateau levels at ≤ 0.2 μg Se/g, so 
sufficient Se should have been present in kidney. Thus, the delayed increase in 
plasma Gpx3 activity suggests that newly synthesized and secreted kidney Gpx3 is 
preferentially retained in kidney or rapidly cleared by binding to basement 
membranes in kidney or in other tissues. This repletion study shows that loss of 
capacity to incorporate Se into Gpx1 in Gpx1 KO mice does not dramatically alter 
expression of other Se biomarkers, nor the short-term flux of Se from intestine 
to liver to kidney.