title: Lrit3 deficient mouse (nob6): a novel model of complete congenital stationary night blindness (cCSNB).
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.
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Neuillé
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
authors.forename: Said
authors.initials: S
authors.lastname: El Shamieh
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Orhan
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Michiels
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Antonio
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Lancelot
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Condroyer
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France; Massachusetts Eye and Ear Infirmary, Ocular Genomics Institute, Boston, Massachusetts, United States of America.
authors.forename: Kinga
authors.initials: K
authors.lastname: Bujakowska
authors.affiliation: Laboratoire de Bioinformatique Intégrative et Génomique, ICube, CNRS, UMR_7357, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, France; Institute of Ophthalmology, University College of London, London, United Kingdom; Fondation Ophtalmologique Adolphe de Rothschild, Paris, France; Académie des Sciences-Institut de France, Paris, France.
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, France; Institute of Ophthalmology, University College of London, London, United Kingdom.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Audo
authors.affiliation: INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000503:physiopathology; D005133:Eye Movements; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000503:physiopathology; D019416:Head Movements; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009216:Myopia / Q000235:genetics* / Q000503:physiopathology; D009755:Night Blindness / Q000235:genetics* / Q000503:physiopathology; D012160:Retina / Q000473:pathology
chemical_list: C000594373:Lrit3 protein, mouse; D008565:Membrane Proteins