PMID- 24598786
OWN - NLM
STAT- MEDLINE
DCOM- 20150113
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 3
DP  - 2014
TI  - Lrit3 deficient mouse (nob6): a novel model of complete congenital stationary 
      night blindness (cCSNB).
PG  - e90342
LID - 10.1371/journal.pone.0090342 [doi]
LID - e90342
AB  - 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.
FAU - Neuille, Marion
AU  - Neuille M
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - El Shamieh, Said
AU  - El Shamieh S
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Orhan, Elise
AU  - Orhan E
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Michiels, Christelle
AU  - Michiels C
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Antonio, Aline
AU  - Antonio A
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      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.
FAU - Lancelot, Marie-Elise
AU  - Lancelot ME
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Condroyer, Christel
AU  - Condroyer C
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
FAU - Bujakowska, Kinga
AU  - Bujakowska K
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      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.
FAU - Poch, Olivier
AU  - Poch O
AD  - Laboratoire de Bioinformatique Integrative et Genomique, ICube, CNRS, UMR_7357, 
      Strasbourg, France.
FAU - Sahel, Jose-Alain
AU  - Sahel JA
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      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; 
      Academie des Sciences-Institut de France, Paris, France.
FAU - Audo, Isabelle
AU  - Audo I
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      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.
FAU - Zeitz, Christina
AU  - Zeitz C
AD  - INSERM, U968, Paris, France; CNRS, UMR_7210, Paris, France; Sorbonne Universites, 
      UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, France.
LA  - eng
SI  - GENBANK/KF954709
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140305
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Lrit3 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - Night blindness, congenital stationary
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Disease Models, Animal
MH  - Eye Diseases, Hereditary/*genetics/physiopathology
MH  - Eye Movements
MH  - Female
MH  - Genetic Diseases, X-Linked/*genetics/physiopathology
MH  - Head Movements
MH  - Male
MH  - Membrane Proteins/*deficiency/genetics
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Myopia/*genetics/physiopathology
MH  - Night Blindness/*genetics/physiopathology
MH  - Retina/pathology
PMC - PMC3943948
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/03/07 06:00
MHDA- 2015/01/15 06:00
PMCR- 2014/03/05
CRDT- 2014/03/07 06:00
PHST- 2013/12/23 00:00 [received]
PHST- 2014/01/31 00:00 [accepted]
PHST- 2014/03/07 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2015/01/15 06:00 [medline]
PHST- 2014/03/05 00:00 [pmc-release]
AID - PONE-D-13-53816 [pii]
AID - 10.1371/journal.pone.0090342 [doi]
PST - epublish
SO  - PLoS One. 2014 Mar 5;9(3):e90342. doi: 10.1371/journal.pone.0090342. eCollection 
      2014.