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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele of Gpdx(a)encoding glucose 6-phosphate dehydrogenase.
Free Radical Biol. Med. 34, 226-232 (2003)
Mice harboring the activity-attenuated Gpdxa-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. Gpdxa-m2Neu is the first hypomorphic allele of a mouse housekeeping gene associated with elevated somatic mutagenesis in vivo
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Glucose 6-phospate dehydrogenase deficiency; Endogenous oxidative stress; In vivo mutagenesis; pUR288; Spleen; Free radicals
ISSN (print) / ISBN
0891-5849
e-ISSN
1873-4596
Zeitschrift
Free Radical Biology and Medicine
Quellenangaben
Band: 34,
Seiten: 226-232
Verlag
Elsevier
Verlagsort
New York, NY
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Human Genetics (IHG)