L-2-oxothiazolidine-4-carboxylate supplementation in murine γ-GT deficiency

γ-glutamyl transpeptidase (γ-GT) deficiency in GGTenu1 mice is associated with glutathionemia, glutathionuria, growth retardation, infertility, lethargy, cataracts, and shortened life span. Total liver glutathione (GSH) content is significantly reduced in γ-GT-deficient mice due to chronic excessive GSH loss. Oral supplementation of GGTenu1 mice with L-2-oxothiazolidine-4-carboxylate (OTZ), a cysteine prodrug, led to partial restoration of liver GSH content. The growth, physical appearance, and behavior of γ-GT-deficient mice were substantially improved following OTZ supplementation. Tissue GSH deficiency is the proximate cause of the phenotypic abnormalities associated with murine γ-GT deficiency.