title: Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina.
abstract: OBJECTIVE
  Previous studies discovered cone phototransduction shutoff occurs normally for Arr1-/- and Arr4-/-; however, it is defective when both visual arrestins are simultaneously not expressed (Arr1-/-Arr4-/-). We investigated the roles of visual arrestins in an all-cone retina (Nrl-/-) since each arrestin has differential effects on visual function, including ARR1 for normal light adaptation, and ARR4 for normal contrast sensitivity and visual acuity.
  
  
  METHODS
  We examined Nrl-/-, Nrl-/-Arr1-/-, Nrl-/-Arr4-/-, and Nrl-/-Arr1-/-Arr4-/- mice with photopic electroretinography (ERG) to assess light adaptation and retinal responses, immunoblot and immunohistochemical localization analysis to measure retinal expression levels of M- and S-opsin, and optokinetic tracking (OKT) to measure the visual acuity and contrast sensitivity.
  
  
  RESULTS
  Study results indicated that Nrl-/- and Nrl-/-Arr4-/- mice light adapted normally, while Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- mice did not. Photopic ERG a-wave, b-wave, and flicker amplitudes followed a general pattern in which Nrl-/-Arr4-/- amplitudes were higher than the amplitudes of Nrl-/-, while the amplitudes of Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- were lower. All three visual arrestin knockouts had faster implicit times than Nrl-/- mice. M-opsin expression is lower when ARR1 is not expressed, while S-opsin expression is lower when ARR4 is not expressed. Although M-opsin expression is mislocalized throughout the photoreceptor cells, S-opsin is confined to the outer segments in all genotypes. Contrast sensitivity is decreased when ARR4 is not expressed, while visual acuity was normal except in Nrl-/-Arr1-/-Arr4-/-.
  
  
  CONCLUSIONS
  Based on the opposite visual phenotypes in an all-cone retina in the Nrl-/-Arr1-/- and Nrl-/-Arr4-/- mice, we conclude that ARR1 and ARR4 perform unique modulatory roles in cone photoreceptors.
authors.affiliation: Mary D. Allen Laboratory for Vision Research, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USC Eye Institute, Los Angeles, California, United States.
authors.forename: Janise D
authors.initials: JD
authors.lastname: Deming
authors.affiliation: Mary D. Allen Laboratory for Vision Research, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USC Eye Institute, Los Angeles, California, United States.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Pak
authors.affiliation: Mary D. Allen Laboratory for Vision Research, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USC Eye Institute, Los Angeles, California, United States 2Department of Anatomy, School of Medicine, Ewha Womans.
authors.forename: Jung-A
authors.initials: JA
authors.lastname: Shin
authors.affiliation: Mary D. Allen Laboratory for Vision Research, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USC Eye Institute, Los Angeles, California, United States.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Brown
authors.affiliation: Rehabilitation Research & Development Center of Excellence, Atlanta VA Medical Center, Decatur, Georgia, United States.
authors.forename: Moon K
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Neuroscience/Ophthalmology, Emory University, Atlanta, Georgia, United States.
authors.forename: Moe H
authors.initials: MH
authors.lastname: Aung
authors.affiliation: Mary D. Allen Laboratory for Vision Research, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USC Eye Institute, Los Angeles, California, United States 5Department of Biomedical Engineering, University of Sou.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Rehabilitation Research & Development Center of Excellence, Atlanta VA Medical Center, Decatur, Georgia, United States 4Neuroscience/Ophthalmology, Emory University, Atlanta, Georgia, United States.
authors.forename: Machelle T
authors.initials: MT
authors.lastname: Pardue
authors.affiliation: Mary D. Allen Laboratory for Vision Research, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USC Eye Institute, Los Angeles, California, United States 6Department of Cell & Neurobiology, Keck School of Medic.
authors.forename: Cheryl Mae
authors.initials: CM
authors.lastname: Craft
mesh_terms: D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D004596:Electroretinography; D015151:Immunoblotting; D007150:Immunohistochemistry; D055537:Light Signal Transduction; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010641:Phenotype; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017299:Rod Opsins / Q000378:metabolism; D014785:Vision, Ocular
chemical_list: D019390:Arrestins; D017299:Rod Opsins; C000607302:arrestin 1 protein, mouse; C000607304:arrestin 4 protein, mouse