Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice.
Document Type
Article
Publication Date
2009
Keywords
Animals, Apoptosis, DNA-Glycosylases, DNA-Modification-Methylases, DNA-Repair, DNA-Repair-Enzymes, Methyl-Methanesulfonate, Methylnitrosourea, Mice, Photoreceptor-Cells-Vertebrate, Retinal-Degeneration, Tumor-Suppressor-Proteins
First Page
888
Last Page
893
JAX Source
Proc Natl Acad Sci U S A 2009 Jan; 106(3):888-93.
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.
Recommended Citation
Meira LB,
Moroski EC,
Green SL,
Calvo JA,
Bronson RT,
Shah D,
Samson LD.
Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice. Proc Natl Acad Sci U S A 2009 Jan; 106(3):888-93.