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Visual Responses in Mice Lacking Critical Components of All Known Retinal Phototransduction Cascades

Allen, AE; Cameron, MA; Brown, TM; Vugler, AA; Lucas, RJ; (2010) Visual Responses in Mice Lacking Critical Components of All Known Retinal Phototransduction Cascades. PLOS ONE , 5 (11) , Article e15063. 10.1371/journal.pone.0015063. Green open access

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Abstract

The mammalian visual system relies upon light detection by outer-retinal rod/cone photoreceptors and melanopsin-expressing retinal ganglion cells. Gnat1(-/-); Cnga3(-/-); Opn4(-/-) mice lack critical elements of each of these photoreceptive mechanisms via targeted disruption of genes encoding rod alpha transducin (Gnat1); the cone-specific alpha 3 cyclic nucleotide gated channel subunit (Cnga3); and melanopsin (Opn4). Although assumed blind, we show here that these mice retain sufficiently widespread retinal photoreception to drive a reproducible flash electroretinogram (ERG). The threshold sensitivity of this ERG is similar to that of cone-based responses, however it is lost under light adapted conditions. Its spectral efficiency is consistent with that of rod opsin, but not cone opsins or melanopsin, indicating that it originates with light absorption by the rod pigment. The TKO light response survives intravitreal injection of U73122 (a phospholipase C antagonist), but is inhibited by a missense mutation of cone alpha transducin (Gnat2(cpfl3)), suggesting Gnat2-dependence. Visual responses in TKO mice extend beyond the retina to encompass the lateral margins of the lateral geniculate nucleus and components of the visual cortex. Our data thus suggest that a Gnat1-independent phototransduction mechanism downstream of rod opsin can support relatively widespread responses in the mammalian visual system. This anomalous rod opsin-based vision should be considered in experiments relying upon Gnat1 knockout to silence rod phototransduction.

Type: Article
Title: Visual Responses in Mice Lacking Critical Components of All Known Retinal Phototransduction Cascades
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0015063
Publisher version: http://dx.doi.org/10.1371/journal.pone.0015063
Language: English
Additional information: © 2010 Allen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The authors have declared that no competing interests exist. This work was supported by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the Your Manchester Fund (to RJL), and The Lincy Foundation and The London Project to Cure Blindness (to AAV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: SIGNALING PATHWAY, CONE TRANSDUCIN, TRANSGENIC MICE, ROD TRANSDUCIN, ALPHA-SUBUNIT, KNOCKOUT MICE, MOUSE, LIGHT, MELANOPSIN, PHOTORECEPTORS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/440820
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