title: Retinal dystrophy resulting from ablation of RXR alpha in the mouse retinal pigment epithelium.
abstract: Vitamin A (retinol) actions in eye development are mediated by retinoic acid receptors (RARs and RXRs). Using the Cre/loxP system, we have selectively ablated RXR alpha in the retinal pigment epithelium (RPE), a cell monolayer critically involved in visual retinoid renewal and phagocytosis of photoreceptor outer segments. In the mutant (RXR alpha (rpe-/-)) mice, RPE cells are morphologically and functionally abnormal and display decreased expression of proteins involved in the visual retinoid cycle, namely RPE65, CRALBP, and RGR. RXR alpha (rpe-/-) mice also show alterations of photoreceptor cells including: 1) decrease in their number; 2) outer segment shortening and disorganization, and 3) reduced light responses in electroretinograms. These results indicate that RXR alpha is required for normal maturation of the RPE, which is known to play essential roles in photoreceptor cell function and survival, and point to a possible involvement of RXR alpha signaling pathways in the RPE in human retinal diseases.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, Collège de France, Strasbourg, France.
authors.forename: Mikiro
authors.initials: M
authors.lastname: Mori
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Serge
authors.initials: S
authors.lastname: Picaud
authors.forename: Colette
authors.initials: C
authors.lastname: Hindelang
authors.forename: Manuel
authors.initials: M
authors.lastname: Simonutti
authors.forename: José
authors.initials: J
authors.lastname: Sahel
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Manuel
authors.initials: M
authors.lastname: Mark
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D004596:Electroretinography; D005123:Eye / Q000196:embryology / Q000254:growth & development; D005136:Eye Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010786:Photoreceptor Cells / Q000473:pathology / Q000648:ultrastructure; D010857:Pigment Epithelium of Eye / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D014176:Protein Biosynthesis; D011506:Proteins; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000172:deficiency* / Q000235:genetics; D012164:Retinal Diseases / Q000209:etiology* / Q000503:physiopathology; D047488:Retinoid X Receptors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C020932:11-cis-retinal-binding protein; C089754:G protein-coupled receptor RGR