Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice |
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| Authors: | Lisiane B. Meira Catherine A. Moroski-Erkul Stephanie L. Green Jennifer A. Calvo Roderick T. Bronson Dharini Shah Leona D. Samson |
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| Affiliation: | aDepartment of Biological Engineering and Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; and ;bRodent Histopathology Laboratory, Harvard Medical School, Boston, MA 02115 |
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| 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. |
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| Keywords: | alkylation damage DNA glycosylase photoreceptors apoptosis |
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