April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
A novel mouse model for complete Congenital Stationary Night Blindness (cCSNB)
Author Affiliations & Notes
  • Marion Neuillé
    Institut de la Vision Univ Pierre et Marie Curie Paris 6; INSERM, UMR_S968; CNRS, UMR_7210, Paris, France
  • Said El Shamieh
    Institut de la Vision Univ Pierre et Marie Curie Paris 6; INSERM, UMR_S968; CNRS, UMR_7210, Paris, France
  • Elise Orhan
    Institut de la Vision Univ Pierre et Marie Curie Paris 6; INSERM, UMR_S968; CNRS, UMR_7210, Paris, France
  • Christelle Michiels
    Institut de la Vision Univ Pierre et Marie Curie Paris 6; INSERM, UMR_S968; CNRS, UMR_7210, Paris, France
  • Kinga Maria Bujakowska
    Institut de la Vision Univ Pierre et Marie Curie Paris 6; INSERM, UMR_S968; CNRS, UMR_7210, Paris, France
    Massachusetts Eye and Ear Infirmary, Ocular Genomics Institute, Boston, MA
  • Olivier Poch
    Integrative Bioinformatics and Genomics Laboratory ICube; CNRS, UMR_7357, Strasbourg, France
  • Jose Alain Sahel
    Univ Pierre et Marie Curie Paris 6; INSERM, UMR_S968; CNRS, UMR_7210; CHNO, INSERM-DHOS CIC 503; Fondation Ophtalmologique Adolphe de Rothschild; Académie des Sciences-Institut de France, Paris, France
    UCL-Institute of Ophthalmology, London, United Kingdom
  • Isabelle Audo
    UCL-Institute of Ophthalmology, London, United Kingdom
    Univ Pierre et Marie Curie Paris 6; INSERM, UMR_S968; CNRS, UMR_7210; CHNO, INSERM-DHOS CIC 503, Paris, France
  • Christina Zeitz
    Institut de la Vision Univ Pierre et Marie Curie Paris 6; INSERM, UMR_S968; CNRS, UMR_7210, Paris, France
  • Footnotes
    Commercial Relationships Marion Neuillé, None; Said El Shamieh, None; Elise Orhan, None; Christelle Michiels, None; Kinga Bujakowska, None; Olivier Poch, None; Jose Sahel, Second Sight (F), UPMC/Essilor (P); Isabelle Audo, None; Christina Zeitz, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1642. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Marion Neuillé, Said El Shamieh, Elise Orhan, Christelle Michiels, Kinga Maria Bujakowska, Olivier Poch, Jose Alain Sahel, Isabelle Audo, Christina Zeitz; A novel mouse model for complete Congenital Stationary Night Blindness (cCSNB). Invest. Ophthalmol. Vis. Sci. 2014;55(13):1642.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: Despite that mutations in LRIT3 lead to autosomal recessive cCSNB, the exact role of the corresponding protein in the ON-bipolar cell signaling cascade remains to be elucidated. To develop a tool to study the function and pathogenic mechanism of LRIT3, we wanted to identify the full length mouse Lrit3 cDNA and genetically and functionally characterize a commercially available Lrit3 knock-out (ko) mouse.

Methods: Mouse retinal mRNA was extracted and full length coding Lrit3 cDNA obtained by RT-PCR. Genomic DNA was isolated and genotyped for the Lrit3 ko allele, common mutations in laboratory mouse strains and known genes underlying cCSNB. The ko model was confirmed on cDNA level. Visual function was measured by Ganzfeld electroretinography. Retinal structure was investigated by fundus auto-fluorescence, histology and spectral domain optical coherence tomography (SD-OCT). The functional characterization was performed at 6 weeks and 6 months.

Results: In contrast to publicly available databases, the mouse Lrit3 cDNA codes for a protein with 681 amino acids instead of 560. We confirmed on DNA and RNA level that with the insertion of a selection cassette a premature stop codon is introduced. This would code for a presumably non-functional short 206 amino acid protein. The mouse line does not harbor other mutations present in common laboratory mouse strains, nor in other cCSNB genes. Lrit3-/- mice exhibit a so called no b-wave (nob) phenotype with an abnormal scotopic electroretinogram (ERG), which lacks the b-wave, whereas the a-wave amplitude and implicit time are normal. The photopic ERG is also altered with severely decreased b-wave amplitude and delayed implicit times for both a- and b-waves. No obvious fundus or histology abnormalities are observed. However, SD-OCT data reveal minor differences with thinned inner nuclear layer and ganglion cell complex. This nob phenotype is noted at 6 weeks and 6 months. Wild-type and heterozygous mice have a normal phenotype at the two time-points.

Conclusions: The stationary nob phenotype of mice lacking Lrit3, which we named Lrit3nob6, confirms the findings previously reported in patients carrying LRIT3 mutations and is similar to other cCSNB mouse models. This study describes a novel mouse model, which will be useful to investigate the pathogenic mechanism associated with LRIT3 mutations and clarify the role of LRIT3 in the ON-bipolar cell signaling cascade.

Keywords: 563 inner retina dysfunction: hereditary • 435 bipolar cells • 510 electroretinography: non-clinical  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×