title: ATR localizes to the photoreceptor connecting cilium and deficiency leads to severe photoreceptor degeneration in mice.
abstract: Ataxia-telangiectasia and Rad3 (ATR), a sensor of DNA damage, is associated with the regulation and control of cell division. ATR deficit is known to cause Seckel syndrome, characterized by severe proportionate short stature and microcephaly. We used a mouse model for Seckel disease to study the effect of ATR deficit on retinal development and function and we have found a new role for ATR, which is critical for the postnatal development of the photoreceptor (PR) layer in mouse retina. The structural and functional characterization of the ATR(+/s) mouse retinas displayed a specific, severe and early degeneration of rod and cone cells resembling some characteristics of human retinal degenerations. A new localization of ATR in the cilia of PRs and the fact that mutant mice have shorter cilia suggests that the PR degeneration here described results from a ciliary defect.
authors.affiliation: Department of Cell Therapy and Regenerative Medicine, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Avda. Americo Vespucio, Seville 41092, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Valdés-Sánchez
authors.forename: Berta
authors.initials: B
authors.lastname: De la Cerda
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Diaz-Corrales
authors.forename: Simone
authors.initials: S
authors.lastname: Massalini
authors.forename: Christina F
authors.initials: CF
authors.lastname: Chakarova
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004195:Disease Models, Animal; D004392:Dwarfism / Q000235:genetics / Q000473:pathology; D019066:Facies; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008831:Microcephaly / Q000235:genetics / Q000473:pathology; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology; D055212:Photoreceptor Connecting Cilium / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000254:growth & development / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; C576897:Atr protein, mouse; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases