dc.contributor.author | Rubio-Fernández, Marcos | |
dc.contributor.author | Uribe, Mary Luz | |
dc.contributor.author | Vicente-Tejedor, Javier | |
dc.contributor.author | Germain, Francisco | |
dc.contributor.author | Susín-Lara, Cristina | |
dc.contributor.author | Quereda, Cristina | |
dc.contributor.author | Montoliu, Lluís | |
dc.contributor.author | Villa, Pedro de la | |
dc.contributor.author | Martín-Nieto, José | |
dc.contributor.author | Cruces, Jesús | |
dc.contributor.other | UAM. Departamento de Bioquímica | es_ES |
dc.contributor.other | Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM) | es_ES |
dc.date.accessioned | 2018-07-11T15:14:43Z | |
dc.date.available | 2018-07-11T15:14:43Z | |
dc.date.issued | 2018-06-01 | |
dc.identifier.citation | Scientific Reports 8.1 (2018): 8543 | en_US |
dc.identifier.issn | 2045-2322 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10486/684084 | |
dc.description.abstract | Hypoglycosylation of α-dystroglycan (α-DG) resulting from deficiency of protein O-mannosyltransferase 1 (POMT1) may cause severe neuromuscular dystrophies with brain and eye anomalies, named dystroglycanopathies. The retinal involvement of these disorders motivated us to generate a conditional knockout (cKO) mouse experiencing a Pomt1 intragenic deletion (exons 3-4) during the development of photoreceptors, mediated by the Cre recombinase expressed from the cone-rod homeobox (Crx) gene promoter. In this mouse, retinal α-DG was unglycosylated and incapable of binding laminin. Retinal POMT1 deficiency caused significant impairments in both electroretinographic recordings and optokinetic reflex in Pomt1 cKO mice, and immunohistochemical analyses revealed the absence of β-DG and of the α-DG-interacting protein, pikachurin, in the outer plexiform layer (OPL). At the ultrastructural level, noticeable alterations were observed in the ribbon synapses established between photoreceptors and bipolar cells. Therefore, O-mannosylation of α-DG in the retina carried out by POMT1 is crucial for the establishment of proper synapses at the OPL and transmission of visual information from cones and rods to their postsynaptic neurons | en_US |
dc.description.sponsorship | This work was funded by the Institute of Health Carlos III (grants PI12/0157 and PI15/073 to J.C. and J.M.-N., PI13/02098 to P.dlV., and RETICS RD12/0034/0006 to P.dlV.), and by the Comunidad de Madrid (‘VISIONANIMAL’ Biomedicine project S2010/BMD2439 to J.C., P.dlV. and L.M.), all of them cofinanced by the European Regional Development Fund (ERDF/FEDER). | en_US |
dc.format.extent | 15 pag. | es_ES |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.ispartof | Scientific Reports | es_ES |
dc.rights | © 2018 The Author(s) | en_US |
dc.subject.other | Hypoglycosylation of α-dystroglycan | en_US |
dc.subject.other | Protein O-mannosyltransferase | en_US |
dc.subject.other | Retinal involvement | en_US |
dc.subject.other | Photoreceptors | en_US |
dc.subject.other | Ribbon synapses | en_US |
dc.title | Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy | en_US |
dc.type | article | en |
dc.subject.eciencia | Medicina | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41598-018-26855-x | es_ES |
dc.identifier.doi | 10.1038/s41598-018-26855-x | es_ES |
dc.identifier.publicationfirstpage | 8543-1 | es_ES |
dc.identifier.publicationissue | 1 | es_ES |
dc.identifier.publicationlastpage | 8543-15 | es_ES |
dc.identifier.publicationvolume | 8 | es_ES |
dc.relation.projectID | Gobierno de España. PI12/0157 | es_ES |
dc.relation.projectID | Comunidad de Madrid. S2010/BMD2439/VISIONANIMAL | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.rights.cc | Reconocimiento | es_ES |
dc.rights.accessRights | openAccess | en |
dc.authorUAM | Cruces Pinto, Jesús (259682) | |
dc.facultadUAM | Facultad de Medicina | |
dc.institutoUAM | Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM) | |