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

• DOI: 10.1038/s41598-018-26855-x
• Publication Date: 2018-05-29T13:24:05Z
• Authors: Marcos Rubio-Fern...; Mary Luz Uribe; Javier Vicente-Te...; Francisco Germain; Cristina Susín-Lara; Cristina Quereda; Lluis Montoliu; Pedro de la Villa; José Martín-Nieto; Jesús Cruces
• Keywords: Conditional gene knockout; Knockout mouse

Abstract Hypoglycosylation of α-dystroglycan (α-DG) resulting from deficiency protein O-mannosyltransferase 1 (POMT1) may cause severe neuromuscular dystrophies with brain and eye anomalies, named dystroglycanopathies. The retinal involvement these disorders motivated us to generate a conditional knockout (cKO) mouse experiencing Pomt1 intragenic deletion (exons 3–4) during the development photoreceptors, mediated by Cre recombinase expressed cone-rod homeobox ( Crx ) gene promoter. In this mouse, α-DG was unglycosylated incapable binding laminin. Retinal POMT1 caused significant impairments in both electroretinographic recordings optokinetic reflex cKO mice, immunohistochemical analyses revealed absence β-DG α-DG-interacting protein, pikachurin, outer plexiform layer (OPL). At ultrastructural level, noticeable alterations were observed ribbon synapses established between photoreceptors bipolar cells. Therefore, O-mannosylation retina carried out is crucial for establishment proper at OPL transmission visual information cones rods their postsynaptic neurons.