Visual responses in mice lacking critical components of all known retinal phototransduction cascades.
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 α transducin (Gnat1); the cone-specific α3 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 α 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.
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Annette E
AE
Allen
Morven A
MA
Cameron
Timothy M
TM
Brown
Anthony A
AA
Vugler
Robert J
RJ
Lucas
D000221:Adaptation, Ocular / Q000187:drug effects; D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism*; D004596:Electroretinography; D004963:Estrenes / Q000494:pharmacology; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism*; D005829:Geniculate Bodies / Q000378:metabolism / Q000502:physiology; D055537:Light Signal Transduction / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D012160:Retina / Q000378:metabolism / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000502:physiology; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D015293:Transducin / Q000235:genetics / Q000378:metabolism*; D014793:Visual Cortex / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D014796:Visual Perception / Q000235:genetics / Q000502:physiology*; D000099210:Melanopsin
D054815:Cyclic Nucleotide-Gated Cation Channels; D004963:Estrenes; D044385:GTP-Binding Protein alpha Subunits; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D017299:Rod Opsins; D015293:Transducin; D000099210:Melanopsin; C518237:Cnga3 protein, mouse; C488949:Gnat1 protein, mouse; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione