title: The loss of transcriptional inhibition by the photoreceptor-cell specific nuclear receptor (NR2E3) is not a necessary cause of enhanced S-cone syndrome.
abstract: OBJECTIVE
  To investigate functional consequence on photoreceptor-cell specific nuclear receptor (NR2E3) transcriptional activity of enhanced S-cone syndrome (ESCS) mutations localized in ligand binding domain (LBD).
  
  
  METHODS
  Point mutations were introduced into the LBD of full length and Gal4 chimeric NR2E3 receptors and transcriptional activity was investigated by using transient co-transfection assay on corresponding luciferase reporters. Expression and DNA binding properties of transfected mutant and wild-type receptors were tested by Western blotting and gel shift assay.
  
  
  RESULTS
  Our analysis show that two ESCS mutations, missense mutations R385P and M407K, abolished NR2E3 repressive activity in the context of full-length and Gal4 chimeric receptors, while W234S and R311Q mutants retained their repressive activity in both assays. All mutant receptors maintained their stability and DNA binding ability.
  
  
  CONCLUSIONS
  These results showed that NR2E3 mutations localized in LBD induce ESCS disease without affecting inhibitory activity as recorded in vitro. This demonstrates the absence of correlation between transcriptional inhibition and ESCS phenotype. This analysis suggests that NR2E3 might have transcriptional activation properties not yet identified.
authors: Inserm U592 Université Pierre et Marie Curie, Laboratoire de Physiopathologie Cellulaire et Moléculaire de la Rétine, Hôpital Saint-Antoine, Paris, France. Mathias.Fradot@st-antoine.inserm.fr <Mathias.Fradot@st-antoine.inserm.fr>
authors: Mathias
authors: M
authors: Fradot
authors: Olivier
authors: O
authors: Lorentz
authors: Jean-Marie
authors: JM
authors: Wurtz
authors: José-Alain
authors: JA
authors: Sahel
authors: Thierry
authors: T
authors: Léveillard
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D005808:Genes, Recessive; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D020125:Mutation, Missense; D057093:Orphan Nuclear Receptors; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells; D012164:Retinal Diseases / Q000235:genetics / Q000503:physiopathology*; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D008024:Ligands; C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D004247:DNA