title: Early-onset, slow progression of cone photoreceptor dysfunction and degeneration in CNG channel subunit CNGB3 deficiency.
abstract: OBJECTIVE
  To investigate the progression of cone dysfunction and degeneration in CNG channel subunit CNGB3 deficiency.
  
  
  METHODS
  Retinal structure and function in CNGB3(-/-) and wild-type (WT) mice were evaluated by electroretinography (ERG), lectin cytochemistry, and correlative Western blot analysis of cone-specific proteins. Cone and rod terminal integrity was assessed by electron microscopy and synaptic protein immunohistochemical distribution.
  
  
  RESULTS
  Cone ERG amplitudes (photopic b-wave) in CNGB3(-/-) mice were reduced to approximately 50% of WT levels by postnatal day 15, decreasing further to approximately 30% of WT levels by 1 month and to approximately 20% by 12 months of age. Rod ERG responses (scotopic a-wave) were not affected in CNGB3(-/-) mice. Average CNGB3(-/-) cone densities were approximately 80% of WT levels at 1 month and declined slowly thereafter to only approximately 50% of WT levels by 12 months. Expression levels of M-opsin, cone transducin α-subunit, and cone arrestin in CNGB3(-/-) mice were reduced by 50% to 60% by 1 month and declined to 35% to 45% of WT levels by 9 months. In addition, cone opsin mislocalized to the outer nuclear layer and the outer plexiform layer in the CNGB3(-/-) retina. Cone and rod synaptic marker expression and terminal ultrastructure were normal in the CNGB3(-/-) retina.
  
  
  CONCLUSIONS
  These findings are consistent with an early-onset, slow progression of cone functional defects and cone loss in CNGB3(-/-) mice, with the cone signaling deficits arising from disrupted phototransduction and cone loss rather than from synaptic defects.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.forename: Lynsie
authors.initials: L
authors.lastname: Morris
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Fliesler
authors.forename: David M
authors.initials: DM
authors.lastname: Sherry
authors.forename: Xi-Qin
authors.initials: XQ
authors.lastname: Ding
mesh_terms: D000818:Animals; D019393:Arrestin / Q000378:metabolism; D015153:Blotting, Western; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000172:deficiency* / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D055355:Opsins / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000378:metabolism* / Q000473:pathology; D015293:Transducin / Q000378:metabolism
chemical_list: D019393:Arrestin; C532622:CNGB3 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D055355:Opsins; D015293:Transducin