Purchase this article with an account.
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)
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.
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.
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.
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.
This PDF is available to Subscribers Only