title: Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.
abstract: BACKGROUND
  Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE), a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells.
  
  
  RESULTS
  Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease.
  
  
  CONCLUSIONS
  Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE.
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, Université de Lyon, Lyon, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Béby
authors.forename: Michael
authors.initials: M
authors.lastname: Housset
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fossat
authors.forename: Coralie
authors.initials: C
authors.lastname: Le Greneur
authors.forename: Frédéric
authors.initials: F
authors.lastname: Flamant
authors.forename: Pierre
authors.initials: P
authors.lastname: Godement
authors.forename: Thomas
authors.initials: T
authors.lastname: Lamonerie
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017353:Gene Deletion; D005838:Genotype; D007150:Immunohistochemistry; D051379:Mice; D046529:Microscopy, Electron, Transmission; D051857:Otx Transcription Factors / Q000235:genetics / Q000502:physiology*; D010786:Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000378:metabolism* / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse