4.6 Article

Lrit3 Deficient Mouse (nob6): A Novel Model of Complete Congenital Stationary Night Blindness (cCSNB)

Journal

PLOS ONE
Volume 9, Issue 3, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0090342

Keywords

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Funding

  1. Agence Nationale de la Recherche [ANR-12-BSVS1-0012-01_GPR179]
  2. Foundation Voir et Entendre
  3. Prix Dalloz for la recherche en ophtalmologie''
  4. Fondation pour la Recherche Medicale (FRM)
  5. Fondation Roland Bailly
  6. Ville de Paris
  7. Region Ile de France
  8. Agence Nationale de la Recherche within the Investissements d'Avenir programme [ANR-11-IDEX-0004-0]
  9. Foundation Fighting Blindness center grant [C-CMM-0907-0428-INSERM04]

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Mutations in LRIT3, coding for a Leucine-Rich Repeat, immunoglobulin-like and transmembrane domains 3 protein lead to autosomal recessive complete congenital stationary night blindness (cCSNB). The role of the corresponding protein in the ON-bipolar cell signaling cascade remains to be elucidated. Here we genetically and functionally characterize a commercially available Lrit3 knock-out mouse, a model to study the function and the pathogenic mechanism of LRIT3. We confirm that the insertion of a Bgeo/Puro cassette in the knock-out allele introduces a premature stop codon, which presumably codes for a non-functional protein. The mouse line does not harbor other mutations present in common laboratory mouse strains or in other known cCSNB genes. Lrit3 mutant mice exhibit a so-called no b-wave (nob) phenotype with lacking or severely reduced b-wave amplitudes in the scotopic and photopic electroretinogram (ERG), respectively. Optomotor tests reveal strongly decreased optomotor responses in scotopic conditions. No obvious fundus auto-fluorescence or histological retinal structure abnormalities are observed. However, spectral domain optical coherence tomography (SD-OCT) reveals thinned inner nuclear layer and part of the retina containing inner plexiform layer, ganglion cell layer and nerve fiber layer in these mice. To our knowledge, this is the first time that SD-OCT technology is used to characterize an animal model for CSNB. This phenotype is noted at 6 weeks and at 6 months. The stationary nob phenotype of mice lacking Lrit3, which we named nob6, confirms the findings previously reported in patients carrying LRIT3 mutations and is similar to other cCSNB mouse models. This novel mouse model will be useful for investigating the pathogenic mechanism(s) associated with LRIT3 mutations and clarifying the role of LRIT3 in the ON-bipolar cell signaling cascade.

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