title: Mice deficient in the Vici syndrome gene Epg5 exhibit features of retinitis pigmentosa.
abstract: Autophagy helps to maintain cellular homeostasis by removing misfolded proteins and damaged organelles, and generally acts as a cytoprotective mechanism for neuronal survival. Here we showed that mice deficient in the Vici syndrome gene Epg5, which is required for autophagosome maturation, show accumulation of ubiquitin-positive inclusions and SQSTM1 aggregates in various retinal cell types. In epg5-/-retinas, photoreceptor function is greatly impaired, and degenerative features including progressively reduced numbers of photoreceptor cells and increased numbers of apoptotic cells in the outer nuclear layer are observed, while the morphology of other parts of the retina is not severely affected. Downstream targets of the unfolded protein response (UPR), including the death inducer DDIT3/CHOP, and also levels of cleaved CASP3 (caspase 3), are elevated in epg5-/-retinas. Thus, apoptotic photoreceptor cell death in epg5-/-retinas may result from the elevated UPR. Our results reveal that Epg5-deficient mice recapitulate key characteristics of retinitis pigmentosa and thus may provide a valuable model for investigating the molecular mechanism of photoreceptor degeneration.
authors.affiliation: a Department of Immunology , Peking University School of Basic Medical Science , Beijing , China.|b State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Guangyan
authors.initials: G
authors.lastname: Miao
authors.affiliation: b State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Yan G
authors.initials: YG
authors.lastname: Zhao
authors.affiliation: b State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: b State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Ji
authors.affiliation: b State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Huayu
authors.initials: H
authors.lastname: Sun
authors.affiliation: a Department of Immunology , Peking University School of Basic Medical Science , Beijing , China.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: b State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D002386:Cataract / Q000235:genetics* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000473:pathology / Q000503:physiopathology; D012162:Retinal Degeneration / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000150:complications / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D056811:Unfolded Protein Response; D033921:Vesicular Transport Proteins
chemical_list: D000071183:Autophagy-Related Proteins; C581266:Epg5 protein, mouse; D011506:Proteins; D033921:Vesicular Transport Proteins
keywords: Epg5; UPR; autophagy; neurodegeneration; retinitis pigmentosa