title: Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice.
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.
authors.affiliation: Department of Biological Engineering and Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Lisiane B
authors.initials: LB
authors.lastname: Meira
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Moroski-Erkul
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Green
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Calvo
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Dharini
authors.initials: D
authors.lastname: Shah
authors.forename: Leona D
authors.initials: LD
authors.lastname: Samson
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D045647:DNA Glycosylases / Q000502:physiology*; D015254:DNA Modification Methylases / Q000502:physiology; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000502:physiology; D008741:Methyl Methanesulfonate / Q000633:toxicity; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects; D012162:Retinal Degeneration / Q000139:chemically induced*; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D000477:Alkylating Agents; D025521:Tumor Suppressor Proteins; D008770:Methylnitrosourea; D008741:Methyl Methanesulfonate; D015254:DNA Modification Methylases; C528331:MGMT protein, mouse; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D045643:DNA Repair Enzymes