Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress

Apurinic/apyrimidinic endonuclease is a key enzyme in the process of base e xcision repair, required for the repair of spontaneous base damage that ari ses as a result of oxidative damage to DNA, In mice, this endonuclease is c oded by the Apex gene, disruption of which is incompatible with embryonic l ife. Here we confirm the embryonic lethality of Apex-null mice and report t he phenotypic characterization of mice that are heterozygous mutants for th e Apex gene (Apex(+/-)). We show that Apex heterozygous mutant cells and an imals are abnormally sensitive to increased oxidative stress, Additionally, such animals manifest elevated levels of oxidative stress markers in serum , and we show that dietary supplementation with antioxidants restores these to normal levels. Apex(+/-) embryos and pups manifest reduced survival tha t can also be partially rescued by dietary supplementation with antioxidant s, These results are consistent with a proposed role for this enzyme in pro tection against the deleterious effects of oxidative stress and raise the p ossibility that humans with heterozygous mutations in the homologous HAP1 g ene may be at increased risk for the phenotypic consequences of oxidative s tress in cells.