Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele of Gpdxa encoding glucose 6-phosphate dehydrogenase
| Autor: | Walter Pretsch, Klaus Felix, Siegfried Janz, Lynne D Rockwood, Georg W. Bornkamm |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Mutant
Mutagenesis (molecular biology technique) lac operon Dehydrogenase Oxidative phosphorylation Glucosephosphate Dehydrogenase medicine.disease_cause Biochemistry Mice chemistry.chemical_compound Physiology (medical) medicine Animals Glucose-6-phosphate dehydrogenase Alleles Sequence Deletion Recombination Genetic Base Sequence biology Molecular biology Enzyme assay Oxidative Stress Lac Operon chemistry Mutagenesis biology.protein Oxidation-Reduction Spleen Oxidative stress |
| Zdroj: | Free Radical Biology and Medicine. 34:226-232 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/s0891-5849(02)01243-1 |
| Popis: | Mice harboring the activity-attenuated Gpdx(a-m2Neu) allele and also harboring a chromosomally integrated lacZ reporter gene to study mutagenesis (pUR288) were used to demonstrate that moderate glucose 6-phosphate dehydrogenase (G6PD) deficiency causes elevated mutagenesis and endogenous oxidative stress in the spleen. G6PD-deficient spleens with a residual enzyme activity of 22% exhibited a dramatic shift in the mutational pattern of lacZ (4.6-fold increase in the prevalence of recombination mutations of lacZ) together with a 1.8-fold increase in mutant frequencies in lacZ. A concomitant 3-fold reduction in catalase activity (dependent upon NADPH) indicated that the in vivo supply of G6PD-generated NADPH was insufficient. An additional 3-fold increase in oxidized glutathione suggested that redox control was disturbed in G6PD-deficient spleens. These findings indicate that G6PD is required for limiting oxidative mutagenesis in the mouse spleen. Gpdx(a-m2Neu) is the first hypomorphic allele of a mouse housekeeping gene associated with elevated somatic mutagenesis in vivo. |
| Databáze: | OpenAIRE |
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