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 tr...
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description | 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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0015063</identifier><identifier>PMID: 21124780</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptation, Ocular - drug effects ; Animals ; Biology ; Cascades ; Cornea ; Critical components ; Cyclic Nucleotide-Gated Cation Channels - genetics ; Cyclic Nucleotide-Gated Cation Channels - metabolism ; Disruption ; Electromagnetic absorption ; Electroretinograms ; Electroretinography ; Estrenes - pharmacology ; Geniculate Bodies - metabolism ; Geniculate Bodies - physiology ; GTP-Binding Protein alpha Subunits - genetics ; GTP-Binding Protein alpha Subunits - metabolism ; Lateral geniculate nucleus ; Life sciences ; Light absorption ; Light effects ; Light Signal Transduction - genetics ; Light Signal Transduction - physiology ; Male ; Mammals ; Medicine ; Melanopsin ; Mice ; Mice, Knockout ; Missense mutation ; Mutation ; Opsins ; Phosphodiesterase Inhibitors - pharmacology ; Phospholipase ; Phospholipase C ; Photoreception ; Photoreceptors ; Phototransduction ; Pyrrolidinones - pharmacology ; Retina ; Retina - metabolism ; Retina - physiology ; Retinal ganglion cells ; Retinal Rod Photoreceptor Cells - metabolism ; Retinal Rod Photoreceptor Cells - physiology ; Rod Opsins - genetics ; Rod Opsins - metabolism ; Rodents ; Signal transduction ; Silence ; Transducin ; Transducin - genetics ; Transducin - metabolism ; Transgenic animals ; Visual cortex ; Visual Cortex - enzymology ; Visual Cortex - metabolism ; Visual Cortex - physiology ; Visual Perception - genetics ; Visual Perception - physiology ; Visual system</subject><ispartof>PloS one, 2010-11, Vol.5 (11), p.e15063</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Allen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Allen et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-546e428a02c16bc012c8eeec5bb37292fd85d4b9fed1d6b7c2fee2d026d1ac343</citedby><cites>FETCH-LOGICAL-c757t-546e428a02c16bc012c8eeec5bb37292fd85d4b9fed1d6b7c2fee2d026d1ac343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993945/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993945/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21124780$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bartell, Paul A.</contributor><creatorcontrib>Allen, Annette E</creatorcontrib><creatorcontrib>Cameron, Morven A</creatorcontrib><creatorcontrib>Brown, Timothy M</creatorcontrib><creatorcontrib>Vugler, Anthony A</creatorcontrib><creatorcontrib>Lucas, Robert J</creatorcontrib><title>Visual responses in mice lacking critical components of all known retinal phototransduction cascades</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Adaptation, Ocular - drug effects</subject><subject>Animals</subject><subject>Biology</subject><subject>Cascades</subject><subject>Cornea</subject><subject>Critical components</subject><subject>Cyclic Nucleotide-Gated Cation Channels - genetics</subject><subject>Cyclic Nucleotide-Gated Cation Channels - metabolism</subject><subject>Disruption</subject><subject>Electromagnetic absorption</subject><subject>Electroretinograms</subject><subject>Electroretinography</subject><subject>Estrenes - pharmacology</subject><subject>Geniculate Bodies - metabolism</subject><subject>Geniculate Bodies - physiology</subject><subject>GTP-Binding Protein alpha Subunits - genetics</subject><subject>GTP-Binding Protein alpha Subunits - metabolism</subject><subject>Lateral geniculate nucleus</subject><subject>Life sciences</subject><subject>Light absorption</subject><subject>Light effects</subject><subject>Light Signal Transduction - 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genetics</subject><subject>Transducin - metabolism</subject><subject>Transgenic animals</subject><subject>Visual cortex</subject><subject>Visual Cortex - enzymology</subject><subject>Visual Cortex - metabolism</subject><subject>Visual Cortex - physiology</subject><subject>Visual Perception - genetics</subject><subject>Visual Perception - physiology</subject><subject>Visual system</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNktuL1DAYxYso7rr6H4gWBMGHGXNrm74Iy-JlYGHBy76G9Es6k9lMMpukXv57U6e7TEHBp4T0d06-npyieI7REtMGv936IThpl3vv9BIhXKGaPihOcUvJoiaIPjzanxRPYtwiVFFe14-LE4IxYQ1Hp4W6NnGQtgw6ZqOoY2lcuTOgSyvhxrh1CcEkAxkBvxvvcimWvi-lteWN8z9cliaTByn3G598CtJFNUAy3pUgI0il49PiUS9t1M-m9az49uH914tPi8urj6uL88sFNFWTFhWrNSNcIgK47gBhAlxrDVXX0Ya0pFe8Uqxre62wqrsGSK81UYjUCkugjJ4VLw--e-ujmAKKAmctwYxXPBOrA6G83Ip9MDsZfgkvjfhz4MNayJB_12rBm4orCrhFqmYYGs5pL3meizOoNB-93k23Dd1OK8jJBGlnpvMvzmzE2n8XpG1py6ps8GoyCP520DH9Y-SJWss8lXH9mDHsTARxzhrKScswydTyL5Qc48-vmZ-tN_l8JngzE2Qm6Z9pLYcYxerL5_9nr67n7OsjdqOlTZvo7TAWIs5BdgAh-BiD7u-Tw0iMDb9LQ4ytE1PDs-zFcer3ortK0990Gvgu</recordid><startdate>20101129</startdate><enddate>20101129</enddate><creator>Allen, Annette E</creator><creator>Cameron, Morven A</creator><creator>Brown, Timothy M</creator><creator>Vugler, Anthony A</creator><creator>Lucas, Robert J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20101129</creationdate><title>Visual responses in mice lacking critical components of all known retinal phototransduction cascades</title><author>Allen, Annette E ; Cameron, Morven A ; Brown, Timothy M ; Vugler, Anthony A ; Lucas, Robert J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-546e428a02c16bc012c8eeec5bb37292fd85d4b9fed1d6b7c2fee2d026d1ac343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adaptation, Ocular - drug effects</topic><topic>Animals</topic><topic>Biology</topic><topic>Cascades</topic><topic>Cornea</topic><topic>Critical components</topic><topic>Cyclic Nucleotide-Gated Cation Channels - genetics</topic><topic>Cyclic Nucleotide-Gated Cation Channels - metabolism</topic><topic>Disruption</topic><topic>Electromagnetic absorption</topic><topic>Electroretinograms</topic><topic>Electroretinography</topic><topic>Estrenes - pharmacology</topic><topic>Geniculate Bodies - metabolism</topic><topic>Geniculate Bodies - physiology</topic><topic>GTP-Binding Protein alpha Subunits - genetics</topic><topic>GTP-Binding Protein alpha Subunits - metabolism</topic><topic>Lateral geniculate nucleus</topic><topic>Life sciences</topic><topic>Light absorption</topic><topic>Light effects</topic><topic>Light Signal Transduction - genetics</topic><topic>Light Signal Transduction - physiology</topic><topic>Male</topic><topic>Mammals</topic><topic>Medicine</topic><topic>Melanopsin</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Missense mutation</topic><topic>Mutation</topic><topic>Opsins</topic><topic>Phosphodiesterase Inhibitors - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21124780</pmid><doi>10.1371/journal.pone.0015063</doi><tpages>e15063</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adaptation, Ocular - drug effects Animals Biology Cascades Cornea Critical components Cyclic Nucleotide-Gated Cation Channels - genetics Cyclic Nucleotide-Gated Cation Channels - metabolism Disruption Electromagnetic absorption Electroretinograms Electroretinography Estrenes - pharmacology Geniculate Bodies - metabolism Geniculate Bodies - physiology GTP-Binding Protein alpha Subunits - genetics GTP-Binding Protein alpha Subunits - metabolism Lateral geniculate nucleus Life sciences Light absorption Light effects Light Signal Transduction - genetics Light Signal Transduction - physiology Male Mammals Medicine Melanopsin Mice Mice, Knockout Missense mutation Mutation Opsins Phosphodiesterase Inhibitors - pharmacology Phospholipase Phospholipase C Photoreception Photoreceptors Phototransduction Pyrrolidinones - pharmacology Retina Retina - metabolism Retina - physiology Retinal ganglion cells Retinal Rod Photoreceptor Cells - metabolism Retinal Rod Photoreceptor Cells - physiology Rod Opsins - genetics Rod Opsins - metabolism Rodents Signal transduction Silence Transducin Transducin - genetics Transducin - metabolism Transgenic animals Visual cortex Visual Cortex - enzymology Visual Cortex - metabolism Visual Cortex - physiology Visual Perception - genetics Visual Perception - physiology Visual system |
title | Visual responses in mice lacking critical components of all known retinal phototransduction cascades |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T00%3A11%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Visual%20responses%20in%20mice%20lacking%20critical%20components%20of%20all%20known%20retinal%20phototransduction%20cascades&rft.jtitle=PloS%20one&rft.au=Allen,%20Annette%20E&rft.date=2010-11-29&rft.volume=5&rft.issue=11&rft.spage=e15063&rft.pages=e15063-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0015063&rft_dat=%3Cgale_plos_%3EA473829412%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1292214858&rft_id=info:pmid/21124780&rft_galeid=A473829412&rft_doaj_id=oai_doaj_org_article_8758d3c190d641c7883fa86bc84c5e88&rfr_iscdi=true |