@article{ebcfb81f263a44a28b4d47714977cb39,
title = "Mislocalization of cone nuclei impairs cone function in mice",
abstract = "The nuclei of cone photoreceptors are located on the apical side of the outer nuclear layer (ONL) in vertebrate retinas. However, the functional role of this evolutionarily conserved localization of cone nuclei is unknown. We previously showed that Linkers of the Nucleoskeleton to the Cytoskeleton (LINC complexes) are essential for the apical migration of cone nuclei during development. Here, we developed an efficient genetic strategy to disrupt cone LINC complexes in mice. Experiments with animals from both sexes revealed that disrupting cone LINC complexes resulted in mislocalization of cone nuclei to the basal side of ONL in mouse retina. This, in turn, disrupted cone pedicle morphology, and appeared to reduce the efficiency of synaptic transmission from cones to bipolar cells. Although we did not observe other developmental or phototransduction defects in cones with mislocalized nuclei, their dark adaptation was impaired, consistent with a deficiency in chromophore recycling. These findings demonstrate that the apical localization of cone nuclei in the ONL is required for the timely dark adaptation and efficient synaptic transmission in cone photoreceptors.",
keywords = "LINC complex, cone photoreceptor, dark adaptation, nucleus migration, retina electrophysiology, retinal degeneration",
author = "Yunlu Xue and David Razafsky and Didier Hodzic and Kefalov, {Vladimir J.}",
note = "Funding Information: This work was funded by the National Eye Institute (EY025696 and EY027387 to VJK, EY022632 to DH, and K99EY030951 to YX), a National Eye Institute Center Core Grant (P30EY002687) and an unrestricted grant to the Washington University Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness. We thank Belinda McMahan and Frank Schottler from the Morphology and Imaging Core of the Department of Ophthalmology and Visual Sciences for their technical support, and the team at the Mouse Genetics Core for handling mice breeding and genotyping. The authors are grateful to Dr Yun‐Zheng Le (University of Oklahoma Health Sciences Center) for sharing the HRGP‐Cre strain, and to Dr Janis Lem (Tufts University) for the Gnat1 strain. We also thank Dr Connie Cepko at Harvard Medical School for insightful comments and constructive feedbacks on this project and manuscript. −/− Funding Information: This work was funded by the National Eye Institute (EY025696 and EY027387 to VJK, EY022632 to DH, and K99EY030951 to YX), a National Eye Institute Center Core Grant (P30EY002687) and an unrestricted grant to the Washington University Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness. We thank Belinda McMahan and Frank Schottler from the Morphology and Imaging Core of the Department of Ophthalmology and Visual Sciences for their technical support, and the team at the Mouse Genetics Core for handling mice breeding and genotyping. The authors are grateful to Dr Yun-Zheng Le (University of Oklahoma Health Sciences Center) for sharing the HRGP-Cre strain, and to Dr Janis Lem (Tufts University) for the Gnat1?/? strain. We also thank Dr Connie Cepko at Harvard Medical School for insightful comments and constructive feedbacks on this project and manuscript. Publisher Copyright: {\textcopyright} 2020 Federation of American Societies for Experimental Biology",
year = "2020",
month = aug,
day = "1",
doi = "10.1096/fj.202000568R",
language = "English",
volume = "34",
pages = "10242--10249",
journal = "FASEB Journal",
issn = "0892-6638",
number = "8",
}