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

L. B. Meira, S. Devaraj, G. E. Kisby, Dennis K Burns, R. L. Daniel, Robert E Hammer, Scott M Grundy, I. Jialal, Errol C Friedberg

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Apurinic/apyrimidinic endonuclease is a key enzyme in the process of base excision repair, required for the repair of spontaneous base damage that arises as a result of oxidative damage to DNA. In mice, this endonuclease is coded by the Apex gene, disruption of which is incompatible with embryonic life. Here we confirm the embryonic lethality of Apex-null mice and report the phenotypic characterization of mice that are heterozygous mutants for the Apex gene (Apex+/-). We show that Apex heterozygous mutant cells and animals 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 that can also be partially rescued by dietary supplementation with antioxidants. These results are consistent with a proposed role for this enzyme in protection against the deleterious effects of oxidative stress and raise the possibility that humans with heterozygous mutations in the homologous HAP1 gene may be at increased risk for the phenotypic consequences of oxidative stress in cells.

Original languageEnglish (US)
Pages (from-to)5552-5557
Number of pages6
JournalCancer Research
Volume61
Issue number14
StatePublished - Jul 15 2001

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Oxidative Stress
Phenotype
Dietary Supplements
Genes
Antioxidants
DNA-(Apurinic or Apyrimidinic Site) Lyase
Endonucleases
Enzymes
DNA Repair
DNA Damage
Embryonic Structures
Biomarkers
Mutation
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress. / Meira, L. B.; Devaraj, S.; Kisby, G. E.; Burns, Dennis K; Daniel, R. L.; Hammer, Robert E; Grundy, Scott M; Jialal, I.; Friedberg, Errol C.

In: Cancer Research, Vol. 61, No. 14, 15.07.2001, p. 5552-5557.

Research output: Contribution to journalArticle

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AU - Daniel, R. L.

AU - Hammer, Robert E

AU - Grundy, Scott M

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