The loss of transcriptional inhibition by the photoreceptor-cell specific nuclear receptor (NR2E3) is not a necessary cause of enhanced S-cone syndrome.

Abstract

PURPOSE:

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: Mathias Fradot, Olivier Lorentz, Jean-Marie Wurtz, José-Alain Sahel, Thierry Léveillard
• Journal: Molecular vision (Mol Vis) Vol. 13 Pg. 594-601 (Apr 06 2007) ISSN: 1090-0535 [Electronic] United States
• PMID: 17438525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• NR2E3 protein, human
• Orphan Nuclear Receptors
• Receptors, Cytoplasmic and Nuclear
• Transcription Factors
• DNA

Topics

• Animals
• COS Cells
• Chlorocebus aethiops
• DNA (metabolism)
• DNA Mutational Analysis
• Genes, Recessive
• HeLa Cells
• Humans
• Ligands
• Mutation, Missense
• Orphan Nuclear Receptors
• Protein Structure, Tertiary
• Receptors, Cytoplasmic and Nuclear (genetics, metabolism)
• Retinal Cone Photoreceptor Cells
• Retinal Diseases (genetics, physiopathology)
• Syndrome
• Transcription Factors (genetics, metabolism)
• Transcription, Genetic
• Transfection