Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa
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http://hdl.handle.net/10045/58982
Títol: | Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa |
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Autors: | Corton, Marta | Ávila-Fernández, Almudena | Campello Blasco, Laura | Sánchez, Mónica | Benavides, Belén | López-Molina, María Isabel | Fernández-Sánchez, Laura | Sánchez-Alcudia, Rocío | Da Silva, Luciana Rodrigues Jacy | Reyes, Noelia | Martín-Garrido, Esther | Zurita, Olga | Fernández-San José, Patricia | Pérez-Carro, Raquel | García-García, Francisco | Dopazo, Joaquín | García-Sandoval, Blanca | Cuenca, Nicolás | Ayuso, Carmen |
Grups d'investigació o GITE: | Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS) |
Centre, Departament o Servei: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Paraules clau: | Retinitis pigmentosa | Photoreceptor degeneration | SAMD11 | Autosomal recessive |
Àrees de coneixement: | Biología Celular |
Data de publicació: | 13-d’octubre-2016 |
Editor: | Macmillan Publishers |
Citació bibliogràfica: | Scientific Reports. 2016, 6: 35370. doi:10.1038/srep35370 |
Resum: | Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors. |
Patrocinadors: | This work was supported by several grants from the Spanish Centre for Biomedical Network Research on Rare Diseases (CIBERER)(06/07/0036), Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Health)/FEDER, including FIS (PI013/00226) and RETICS (RD09/0076/00101 and RD12/0034/0010), Ministry of Economy and Competitiveness (MINECO), including FEDER (BFU2012-36845), and BIO2011-27069, Conselleria de Educació of the Valencia Community (PROMETEOII/2014/025), Spanish National Organization of the Blind (ONCE) and the Spanish Fighting Blindness Foundation (FUNDALUCE). M.C. was sponsored by the Miguel Servet Program for Researchers in the Spanish National Health Service (CP12/03256) and RSA by Sara Borrel Postdoctoral Program (CD12/00676), both from the ISCIII/FEDER. A.A-F. was sponsored by CIBERER, RPC is supported by Fundación Conchita Rábago (FCR), L.C is sponsored by RETICS (RD12/0034/0010) from ISCIII and L.d.S. was supported by CAPES Foundation, Ministry of Education of Brazil. |
URI: | http://hdl.handle.net/10045/58982 |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep35370 |
Idioma: | eng |
Tipus: | info:eu-repo/semantics/article |
Drets: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Revisió científica: | si |
Versió de l'editor: | http://dx.doi.org/10.1038/srep35370 |
Apareix a la col·lecció: | INV - NEUROVIS - Artículos de Revistas |
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