Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele of Gpdx(a) encoding glucose 6-phosphate dehydrogenase

Klaus Felix; Lynne D Rockwood; Walter Pretsch; Georg Wilhelm Bornkamm; Siegfried Janz

doi:10.1016/S0891-5849(02)01243-1

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Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele of Gpdx(a) encoding glucose 6-phosphate dehydrogenase

Journal article

Peer reviewed

Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele of Gpdx(a) encoding glucose 6-phosphate dehydrogenase

Klaus Felix, Lynne D Rockwood, Walter Pretsch, Georg Wilhelm Bornkamm and Siegfried Janz

Free radical biology & medicine, Vol.34(2), pp.226-232

01/15/2003

DOI: 10.1016/S0891-5849(02)01243-1

PMID: 12521604

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Abstract

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.

Oxidation-Reduction

Oxidative Stress

Lac Operon - genetics

Animals

Mutagenesis

Spleen - enzymology

Spleen - metabolism

Base Sequence

Alleles

Glucosephosphate Dehydrogenase - metabolism

Recombination, Genetic - genetics

Mice

Glucosephosphate Dehydrogenase - genetics

Sequence Deletion - genetics

Details

Title: Subtitle: Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele of Gpdx(a) encoding glucose 6-phosphate dehydrogenase
Creators: Klaus Felix - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Lynne D Rockwood
Walter Pretsch
Georg Wilhelm Bornkamm
Siegfried Janz
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.34(2), pp.226-232
DOI: 10.1016/S0891-5849(02)01243-1
PMID: 12521604
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Language: English
Date published: 01/15/2003
Academic Unit: Pathology
Record Identifier: 9984083850002771

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