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Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice

Author:
Meira, Lisiane B., Moroski-Erkul, Catherine A., Green, Stephanie L., Calvo, Jennifer A., Bronson, Roderick T., Shah, Dharini, Samson, Leona D.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2009 v.106 no.3 pp. 888-893
ISSN:
0027-8424
Subject:
Americans, DNA, DNA repair, alkylation, apoptosis, environmental factors, gene expression, genes, heterozygosity, macular degeneration, mice, phenotype, photoreceptors, retina, vision
Abstract:
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.
Agid:
2362994