Retinal dystrophy resulting from ablation of RXR alpha in the mouse retinal pigment epithelium.
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.
Mori
Mikiro
M
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.
Metzger
Daniel
D
Picaud
Serge
S
Hindelang
Colette
C
Simonutti
Manuel
M
Sahel
José
J
Chambon
Pierre
P
Mark
Manuel
M
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
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