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- Title
A New CRB1 Rat Mutation Links Müller Glial Cells to Retinal Telangiectasia.
- Authors
Min Zhao; Andrieu-Soler, Charlotte; Kowalczuk, Laura; Cortés, María Paz; Berdugo, Marianne; Dernigoghossian, Marilyn; Halili, Francisco; Jeanny, Jean-Claude; Goldenberg, Brigitte; Savoldelli, Michèle; Sanharawi, Mohamed El; Naud, Marie-Christine; van Ijcken, Wilfred; Pescini-Gobert, Rosanna; Martinet, Danielle; Maass, Alejandro; Wijnholds, Jan; Crisanti, Patricia; Rivolta, Carlo; Behar-Cohen, Francine
- 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.
- Subjects
NEUROGLIA; TELANGIECTASIA; ADHERENS junctions; PHOTORECEPTORS; LABORATORY rats; GENETIC mutation
- Publication
Journal of Neuroscience, 2015, Vol 35, Issue 15, p6093
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3412-14.2015