Visual responses in mice lacking critical components of all known retinal phototransduction cascades
Open accessAbstract
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.
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The retained sensitivity to high irradiance UV light in Gnat1/2-dKO mice was most likely caused by incomplete loss of cone-based vision in this model.
“which was most likely caused by incomplete loss of cone-based vision in this model (Allen et al., 2010).”
From Ventral striatum dopamine release encodes unique properties of visual stimuli in mice (2023) · cites this paper as Allen et al., 2010
The Results section ('A role for Gnat2 in the TKO ERG?'; page unavailable) reports a residual response to bright flashes in Gnat1−/−;Gnat2cpfl3/cpfl3 mice and says it probably originates in cones. The reported flashes were white, not UV, so the paper does not establish that the retained sensitivity specifically to high-irradiance UV light has this cause. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSpectral analysis indicated that Gnat1/2-dKO mice retain sensitivity to UV light, which may be indicative of residual cone-based vision.
“Spectral analysis indicated that Gnat1/2-dKO mice retain sensitivity to UV light (Figure 4D, Figure 4—figure supplement 1), which may be indicative of residual cone-based vision (Allen et al., 2010).”
From Ventral striatum dopamine release encodes unique properties of visual stimuli in mice (2023) · cites this paper as Allen et al., 2010
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Self-citationTeikari, P. (2012) · theses.fr (ABES) · doi:10.70675/96362824z0120z4ed7z94c7zb60f3d7e5f50 · Cited by 2 · see citing works
Nishiguchi, K. M., Fujita, K., Katayama, S., & Nakazawa, T. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/552653 · Cited by 1 · see citing works
Quantum Mechanics of the Cell: An Emerging Field
Ashrafuzzaman, M. (2018) · Springer eBooks · doi:10.1007/978-3-319-77465-7_9
Rod Photoreceptor Activation Alone Defines the Release of Dopamine in the RetinaPreprint
Pérez-Fernández, V., Milosavljevic, N., Allen, A. E., Vessey, K. A., Jobling, A. I., Fletcher, E. L., Morley, J. W., & Cameron, M. A. (2018) · SSRN Electronic Journal · doi:10.2139/ssrn.3284451
Self-citationShim, H., & Chen, C.-K. (2012) · Springer eBooks · doi:10.1007/978-1-4419-0461-4_587
Shim, H., & Chen, C.-K. (2017) · Springer eBooks · doi:10.1007/978-3-319-67199-4_587
Melanopsin Ganglion Cells in the Mouse Retina Independently Evoke Pupillary Light ReflexPreprint
Bohl, J. M., Hassan, A. R., Sharpe, Z. J., Kola, M., Ayub, M., Pandey, Y., Shehu, A., & Ichinose, T. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.2139/ssrn.4615443
Examining the role of the photopigment melanopsin in the striatal dopamine response to light
Gonzalez, L. S., Fisher, A. A., Grover, K. E., & Robinson, J. E. (2025) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2025.1568878
Bałamut, B., Węgrzyn, P., Posluszny, A., & Foik, A. T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.07.680926
- Authors
- Allen, A. E., Cameron, M. A., Brown, T. M., Vugler, A. A., & Lucas, R. J.
- Affiliations
- University of Manchester (GB)
- University College London (GB)
- Corresponding author
- Lucas, Robert J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-11-29
- Volume
- 5
- Issue
- 11
- Pages
- e15063
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2993945
- OpenAlex
- W2046609408
- Cited by
- 64
- References
- 33
- Citations by year
- 2025: 3 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 8
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Lincy Foundation
- Wellcome Trust
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- rod phototransduction, GNAT2, CNGA3, melanopsin, rod photoreceptors, flash electroretinogram, light adaptation, rod opsin, phospholipase C, lateral geniculate nucleus, visual cortex, mouse visual system
- MeSH terms
- Melanopsin, Adaptation, Ocular, Animals, Electroretinography, Estrenes, Geniculate Bodies, Male, Phosphodiesterase Inhibitors, Pyrrolidinones, Retina, Visual Cortex, Visual Perception, Transducin, Rod Opsins, Retinal Rod Photoreceptor Cells, Mice, Knockout, GTP-Binding Protein alpha Subunits, Mice, Cyclic Nucleotide-Gated Cation Channels, Light Signal Transduction
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