Exon 3 was replaced with a modified one in which two point mutations result in the amino acid substitution of a serine for selenocysteine at position 46 (U46S). A floxed neomycin resistance cassette was inserted downstream of exon 7. Immunoblot analysis revealed a significant up-regulation of Gpx4 protein levels in all somatic tissues of heterozygous mutant mice; however, significantly decreased levels of Gpx4-specific activities were detectable only in heterozygous livers, whereas no difference was seen in kidney, brain and heart. (J:225651)