Open AccessAag-initiated base excision repair drives alkylation-induced retinal degeneration in mice
Author(s) -
Lisiane B. Meira,
Catherine A. Moroski-Erkul,
Stephanie L. Green,
Jennifer A. Calvo,
Roderick T. Bronson,
Dharini Shah,
Leona D. Samson
Publication year - 2009
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0807030106
Subject(s) - retinal degeneration , biology , dna glycosylase , haploinsufficiency , base excision repair , dna repair , retinal , transgene , degeneration (medical) , dna damage , retinitis pigmentosa , microbiology and biotechnology , genetically modified mouse , genetics , gene , dna , phenotype , biochemistry , pathology , medicine
Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA repair protein alkyladenine DNA glycosylase (Aag) in both differentiating and postmitotic retinas. Moreover, transgenic expression of Aag activity restores the alkylation sensitivity of photoreceptors in Aag null animals. Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype.
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