title: A new CRB1 rat mutation links Müller glial cells to retinal telangiectasia.
abstract: We have identified and characterized a spontaneous Brown Norway from Janvier rat strain (BN-J) presenting a progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of retinal Müller glial cells resembling human macular telangiectasia type 2 (MacTel 2), which is a retinal disease of unknown cause. Genetic analyses showed that the BN-J phenotype results from an autosomal recessive indel novel mutation in the Crb1 gene, causing dislocalization of the protein from the retinal Müller glia (RMG)/photoreceptor cell junction. The transcriptomic analyses of primary RMG cultures allowed identification of the dysregulated pathways in BN-J rats compared with wild-type BN rats. Among those pathways, TGF-β and Kit Receptor Signaling, MAPK Cascade, Growth Factors and Inflammatory Pathways, G-Protein Signaling Pathways, Regulation of Actin Cytoskeleton, and Cardiovascular Signaling were found. Potential molecular targets linking RMG/photoreceptor interaction with the development of retinal telangiectasia are identified. This model can help us to better understand the physiopathologic mechanisms of MacTel 2 and other retinal diseases associated with telangiectasia.
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Min
authors: http://orcid.org/0000-0002-5418-7275
authors: M
authors: Zhao
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Charlotte
authors: http://orcid.org/0000-0002-3287-6117
authors: C
authors: Andrieu-Soler
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Laura
authors: http://orcid.org/0000-0003-0268-9430
authors: L
authors: Kowalczuk
authors: Department of Mathematical Engineering, Center for Mathematical Modeling (Unité Mixte Internationale 2807-Centre National de la Recherche Scientifique) and Funds for Advanced Studies in Priority Areas (FONDAP) Center for Genome Regulation, Faculty of Mathematical and Physical Sciences, University of Chile, Santiago 8320000, Chile.
authors: María
authors: M
authors: Paz Cortés
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Marianne
authors: http://orcid.org/0000-0002-4299-837X
authors: M
authors: Berdugo
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Marilyn
authors: M
authors: Dernigoghossian
authors: Ophthalmic Biophysics Center, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida 33136.
authors: Francisco
authors: F
authors: Halili
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Jean-Claude
authors: JC
authors: Jeanny
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Brigitte
authors: B
authors: Goldenberg
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Michèle
authors: M
authors: Savoldelli
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Mohamed
authors: M
authors: El Sanharawi
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Marie-Christine
authors: MC
authors: Naud
authors: Center for Biomics, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.
authors: Wilfred
authors: W
authors: van Ijcken
authors: Department of Medical Genetics, University of Lausanne, 1005 Lausanne, Switzerland.
authors: Rosanna
authors: R
authors: Pescini-Gobert
authors: Service of Medical Genetics, Lausanne University Hospital, 1011, Lausanne, Switzerland.
authors: Danielle
authors: D
authors: Martinet
authors: Department of Mathematical Engineering, Center for Mathematical Modeling (Unité Mixte Internationale 2807-Centre National de la Recherche Scientifique) and Funds for Advanced Studies in Priority Areas (FONDAP) Center for Genome Regulation, Faculty of Mathematical and Physical Sciences, University of Chile, Santiago 8320000, Chile.
authors: Alejandro
authors: A
authors: Maass
authors: Department of Neuromedical Genetics, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands, and.
authors: Jan
authors: http://orcid.org/0000-0003-0099-460X
authors: J
authors: Wijnholds
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France.
authors: Patricia
authors: http://orcid.org/0000-0002-7578-0748
authors: P
authors: Crisanti
authors: Department of Medical Genetics, University of Lausanne, 1005 Lausanne, Switzerland.
authors: Carlo
authors: C
authors: Rivolta
authors: INSERM Unité Mixte de Recherche Scientifique 1138, Team 17, Centre de Recherche des Cordeliers, 75006 Paris, France, Pierre and Marie Curie University, 75005 Paris, France, Paris Descartes University, 75006 Paris, France, Department of Ophthalmology of University of Lausanne, Jules Gonin Hospital, Fondation Asile des Aveugles, 1000 Lausanne, Switzerland francine.behar@gmail.com.
authors: Francine
authors: F
authors: Behar-Cohen
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004596:Electroretinography; D063928:Ependymoglial Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005451:Fluorescein Angiography; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D012162:Retinal Degeneration / Q000209:etiology / Q000235:genetics / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology; D013684:Telangiectasis / Q000150:complications* / Q000235:genetics*; D014795:Visual Pathways / Q000473:pathology / Q000648:ultrastructure
chemical_list: D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: adherens junction; disease model; genetics; microcirculation; retinal blood vessels; retinal degeneration