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Alterations in the ribbon synapse of the first Pomt1 conditional knockout mouse model of dystroglycanopathies

AuthorsRubio, Marcos; Uribe, Mary Luz; Vicente, Javier; Susín, Cristina ; Martín-Nieto, José; Cruces, Jesús
Issue Date2016
CitationXXXIX Congreso de la SEBBM (2016)
AbstractProtein O-mannosyltransferase 1 (POMT1) is one of the causative genes of dystroglycanopathies (DGPs), a heterogeneous group of congenital recessive neuromuscular diseases. The most severe DGPs course with important muscular, brain and ocular anomalies derived from hypoglycosylation of α−dystroglycan (α−DG), a key protein component of the dystrophin-glycoprotein complex (DGC) in muscular and neural cells. α−DG interacts with extracelular matrix (ECM) proteins by means of its O-glycosylated residues, specifically O-mannosyl glycans, whose initial mannose is covalently added by POMT1. Our group has previously evidenced the embryonic lethality of a Pomt1 constitutive knockout (KO) mutation. Consequently, in this work we generated, by using the Cre-loxP system, a retinal conditional KO (cKO) mouse model selectively undergoing a Pomt1 intragenic deletion in developing photoreceptors. Lack of POMT1 in the retinas of these mice correlated with a loss of α−DG glycosylation and laminin-binding ability. Electroretinographic (ERG) records in Pomt1 cKO mice showed a significantly reduced b-wave amplitude and increased implicit time. By immunohistofluorescence, β-DG and pikachurin (a retinal ECM, α−DG-interacting-protein) were found to be absent in the outer plexiform layer (OPL), and a sprouting of bipolar cell dendrites into the outer nuclear layer was observed. Finally, at the ultrastructural level ribbon synapses exhibited an anomalous organization, with bipolar cells processes being barely visible in the synaptic cleft of cones and rods axon terminals. In conclusion, our findings are strongly suggestive of a pivotal role of POMT1 and α−DG glycosylation in the formation and function of ribbon synapses between photoreceptors and bipolar cells in the OPL.
DescriptionResumen del póster presentado al XXXIX Congreso anual de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca, del 5 al 8 de septiembre 2016.-- et al.
Appears in Collections:(IIBM) Comunicaciones congresos
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