Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy

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 knock...

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Autores: Rubio-Fernández, Marcos, Uribe, Mary Luz, Vicente-Tejedor, Javier, Germain, Francisco, Susín-Lara, Cristina, Quereda, Cristina, Montoliu, Lluís, Villa, Pedro de la, Martín-Nieto, José, Cruces, Jesús
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/684084
Acceso en línea:http://hdl.handle.net/10486/684084
https://dx.doi.org/10.1038/s41598-018-26855-x
Access Level:acceso abierto
Palabra clave:Hypoglycosylation of α-dystroglycan
Protein O-mannosyltransferase
Retinal involvement
Photoreceptors
Ribbon synapses
Medicina
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spelling Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathyRubio-Fernández, MarcosUribe, Mary LuzVicente-Tejedor, JavierGermain, FranciscoSusín-Lara, CristinaQuereda, CristinaMontoliu, LluísVilla, Pedro de laMartín-Nieto, JoséCruces, JesúsHypoglycosylation of α-dystroglycanProtein O-mannosyltransferaseRetinal involvementPhotoreceptorsRibbon synapsesMedicinaHypoglycosylation 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 neuronsThis 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).Nature Publishing GroupDepartamento de BioquímicaFacultad de MedicinaInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)20182018-06-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/684084https://dx.doi.org/10.1038/s41598-018-26855-xreponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6840842026-06-23T12:46:27Z
dc.title.none.fl_str_mv Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy
title Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy
spellingShingle Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy
Rubio-Fernández, Marcos
Hypoglycosylation of α-dystroglycan
Protein O-mannosyltransferase
Retinal involvement
Photoreceptors
Ribbon synapses
Medicina
title_short Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy
title_full Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy
title_fullStr Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy
title_full_unstemmed Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy
title_sort Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy
dc.creator.none.fl_str_mv Rubio-Fernández, Marcos
Uribe, Mary Luz
Vicente-Tejedor, Javier
Germain, Francisco
Susín-Lara, Cristina
Quereda, Cristina
Montoliu, Lluís
Villa, Pedro de la
Martín-Nieto, José
Cruces, Jesús
author Rubio-Fernández, Marcos
author_facet Rubio-Fernández, Marcos
Uribe, Mary Luz
Vicente-Tejedor, Javier
Germain, Francisco
Susín-Lara, Cristina
Quereda, Cristina
Montoliu, Lluís
Villa, Pedro de la
Martín-Nieto, José
Cruces, Jesús
author_role author
author2 Uribe, Mary Luz
Vicente-Tejedor, Javier
Germain, Francisco
Susín-Lara, Cristina
Quereda, Cristina
Montoliu, Lluís
Villa, Pedro de la
Martín-Nieto, José
Cruces, Jesús
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Bioquímica
Facultad de Medicina
Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
dc.subject.none.fl_str_mv Hypoglycosylation of α-dystroglycan
Protein O-mannosyltransferase
Retinal involvement
Photoreceptors
Ribbon synapses
Medicina
topic Hypoglycosylation of α-dystroglycan
Protein O-mannosyltransferase
Retinal involvement
Photoreceptors
Ribbon synapses
Medicina
description 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
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-06-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/684084
https://dx.doi.org/10.1038/s41598-018-26855-x
url http://hdl.handle.net/10486/684084
https://dx.doi.org/10.1038/s41598-018-26855-x
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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