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Tetracycline‐dependent regulation of formamidopyrimidine DNA glycosylase in transgenic mice conditionally reduces oxidative DNA damage in vivo
Author(s) -
Laposa Rebecca R.,
Henderson Jeffrey T.,
Wells Peter G.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0689fje
Subject(s) - dna glycosylase , dna damage , dna repair , neurodegeneration , transgene , genetically modified mouse , oxidative stress , dna , dna oxidation , chemistry , doxycycline , base excision repair , biology , microbiology and biotechnology , biochemistry , gene , medicine , pathology , disease , antibiotics
8‐Oxo‐deoxyguanosine (8‐oxo‐dG) is a pervasive oxidative DNA lesion formed by endogenous oxidative stress and enhanced by drugs and environmental chemicals. This lesion results in transcriptional errors and mutations and is linked to neurodegeneration, teratogenesis, cancer, and other pathologies. We demonstrate that the neonatal central nervous system of transgenic mice carrying the tetracycline‐regulable DNA repair gene formamidopyrimidine DNA glycosylase ( fpg ) has a 50% reduction in 8‐oxo‐dG levels. This enhanced DNA repair is suppressed by treatment with doxycycline. For the first time, this murine model permits the level of a specific DNA oxidation product to be regulated in a temporally and spatially specific manner, allowing its role as a primary or secondary factor in neurodegenerative disease to be determined in vivo .