title: Impairment of Vision in a Mouse Model of Usher Syndrome Type III.
abstract: OBJECTIVE
  The purpose of this study was to obtain an Usher syndrome type III mouse model with retinal phenotype.
  
  
  METHODS
  Speed congenic method was used to obtain Clrn1 exon 1 knockout (Clrn1-/-) and Clrn1N48K knockin (Clrn1N48K/N48K) mice under A/J background. To study the retinal functions of these mice, we measured scotopic and photopic ERG responses. To observe if there are any structural abnormalities, we conducted light and transmission electron microscopy of fixed retinal specimens.
  
  
  RESULTS
  In 3-month-old Clrn1-/- mice, scotopic b-wave amplitude was reduced by more than 25% at the light intensities from -2.2 to 0.38 log cd·s/m2, but scotopic a-wave amplitudes were comparable to those of age-matched wild type mice at all the light intensities tested. In 9-month-old Clrn1-/- mice, scotopic b-wave amplitudes were further reduced by more than 35%, and scotopic a-wave amplitude also showed a small decline as compared with wild type mice. Photopic ERG responses were comparable between Clrn1-/- and wild type mice. Those electrophysiological defects were not associated with a loss of rods. In Clrn1N48K/N48K mice, both a- and b-wave amplitudes were not discernable from those of wild type mice aged up to 10 months.
  
  
  CONCLUSIONS
  Mutations that are Clrn1-/- biallelic cause visual defects when placed under A/J background. The absence of apparent rod degeneration suggests that the observed phenotype is due to functional defects, and not due to loss of rods. Biallelic Clrn1N48K/N48K mutations did not cause discernible visual defects, suggesting that Clrn1- allele is more severely dysfunctional than ClrnN48K allele.
authors.forename: Guilian
authors.initials: G
authors.lastname: Tian
authors.forename: Richard
authors.initials: R
authors.lastname: Lee
authors.forename: Philip
authors.initials: P
authors.lastname: Ropelewski
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Imanishi
mesh_terms: D000818:Animals; D055253:Color Vision / Q000502:physiology*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D003623:Dark Adaptation / Q000502:physiology*; D004195:Disease Models, Animal; D004596:Electroretinography; D005838:Genotype; D015151:Immunoblotting; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D016133:Polymerase Chain Reaction; D012160:Retina / Q000503:physiopathology* / Q000648:ultrastructure; D052245:Usher Syndromes / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D014786:Vision Disorders / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: C512668:Clrn1 protein, mouse; D008565:Membrane Proteins; D004247:DNA