Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy
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Título: | Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy |
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Autor/es: | Rubio-Fernández, Marcos | Uribe, Mary Luz | Vicente-Tejedor, Javier | Germain, Francisco | Susín-Lara, Cristina | Quereda, Cristina | Montoliu, Lluis | Villa, Pedro de la | Martín-Nieto, José | Cruces, Jesús |
Grupo/s de investigación o GITE: | Genética Humana y de Mamíferos (GHM) |
Centro, Departamento o Servicio: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología | Universidad de Alicante. Instituto Multidisciplinar para el Estudio del Medio "Ramón Margalef" |
Palabras clave: | Photoreceptor ribbon synapses | Pomt1 | Conditional knockout | Mouse model | Dystroglycanopathy |
Área/s de conocimiento: | Genética |
Fecha de publicación: | 4-jun-2018 |
Editor: | Springer Nature |
Cita bibliográfica: | Scientific Reports. 2018, 8: 8543. doi:10.1038/s41598-018-26855-x |
Resumen: | 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. |
Patrocinador/es: | 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). |
URI: | http://hdl.handle.net/10045/76428 |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-018-26855-x |
Idioma: | eng |
Tipo: | info:eu-repo/semantics/article |
Derechos: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Revisión científica: | si |
Versión del editor: | https://doi.org/10.1038/s41598-018-26855-x |
Aparece en las colecciones: | INV - GHM - Artículos de Revistas |
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