Lrit3 deficient mouse (nob6): a novel model of complete congenital stationary night blindness (cCSNB)

PLoS One. 2014 Mar 5;9(3):e90342. doi: 10.1371/journal.pone.0090342. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Disease Models, Animal
  • Eye Diseases, Hereditary / genetics*
  • Eye Diseases, Hereditary / physiopathology
  • Eye Movements
  • Female
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / physiopathology
  • Head Movements
  • Male
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Myopia / genetics*
  • Myopia / physiopathology
  • Night Blindness / genetics*
  • Night Blindness / physiopathology
  • Retina / pathology

Substances

  • Lrit3 protein, mouse
  • Membrane Proteins

Supplementary concepts

  • Night blindness, congenital stationary

Associated data

  • GENBANK/KF954709

Grants and funding

The project was supported by Agence Nationale de la Recherche [ANR-12-BSVS1-0012-01_GPR179] (CZ), Foundation Voir et Entendre (CZ), Prix Dalloz for “la recherche en ophtalmologie” (CZ), The Fondation pour la Recherche Médicale (FRM) in partnership with the Fondation Roland Bailly (CZ), Ville de Paris and Région Ile de France, LABEX LIFESENSES [reference ANR-10-LABX-65] supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir programme [ANR-11-IDEX-0004-0], Foundation Fighting Blindness center grant [C-CMM-0907-0428-INSERM04]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.