Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele of Gpdx(a) encoding glucose 6-phosphate dehydrogenase. Free Radic Biol Med 2003 Jan 15;34(2):226-32
Date
01/11/2003Pubmed ID
12521604DOI
10.1016/s0891-5849(02)01243-1Scopus ID
2-s2.0-0037438878 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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.
Author List
Felix K, Rockwood LD, Pretsch W, Bornkamm GW, Janz SAuthor
Siegfried Janz MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AllelesAnimals
Base Sequence
Glucosephosphate Dehydrogenase
Lac Operon
Mice
Mutagenesis
Oxidation-Reduction
Oxidative Stress
Recombination, Genetic
Sequence Deletion
Spleen
