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Some of these dominant rod opsin mutant proteins, which desensitize transgenic<jats:italic>Xenopus<\/jats:italic>rods, provide an animal model for congenital night blindness. In a genetic screen to identify retinal degeneration mutants in<jats:italic>Drosophila<\/jats:italic>, we identified a dominant mutation in the<jats:italic>ninaE<\/jats:italic>gene (<jats:italic>NinaE<jats:sup>pp100<\/jats:sup><\/jats:italic>) that encodes the rhodopsin that is expressed in photoreceptors R1-R6. Deep pseudopupil analysis and histology showed that the degeneration was attributable to a light-independent apoptosis. Whole-cell recordings revealed that the<jats:italic>NinaE<jats:sup>pp100<\/jats:sup><\/jats:italic>mutant photoreceptor cells were strongly desensitized, which partially masked their constitutive activity. This desensitization primarily resulted from both the persistent binding of arrestin (ARR2) to the NINAE<jats:sup>pp100<\/jats:sup>mutant opsin and the constitutive activity of the phototransduction cascade. Whereas mutations in several<jats:italic>Drosophila<\/jats:italic>genes other than<jats:italic>ninaE<\/jats:italic>were shown to induce photoreceptor cell apoptosis by stabilizing a rhodopsin-arrestin complex,<jats:italic>NinaE<jats:sup>pp100<\/jats:sup><\/jats:italic>represented the first rhodopsin mutation that stabilized this protein complex. Additionally, the<jats:italic>NinaE<jats:sup>pp100<\/jats:sup><\/jats:italic>mutation led to elevated levels of G<jats:sub>q<\/jats:sub>\u03b1 in the cytosol, which mediated a novel retinal degeneration pathway. Eliminating both G<jats:sub>q<\/jats:sub>\u03b1 and arrestin completely rescued the<jats:italic>NinaE<jats:sup>pp100<\/jats:sup><\/jats:italic>-dependent photoreceptor cell death, which indicated that the degeneration is entirely dependent on both G<jats:sub>q<\/jats:sub>\u03b1 and arrestin. Such a combination of multiple pathological pathways resulting from a single mutation may underlie several dominant retinal diseases in humans.<\/jats:p>","DOI":"10.1523\/jneurosci.5426-03.2004","type":"journal-article","created":{"date-parts":[[2004,3,10]],"date-time":"2004-03-10T22:52:59Z","timestamp":1078959179000},"page":"2516-2526","source":"Crossref","is-referenced-by-count":30,"title":["Novel Dominant Rhodopsin Mutation Triggers Two Mechanisms of Retinal Degeneration and Photoreceptor Desensitization"],"prefix":"10.1523","volume":"24","author":[{"given":"Roustem","family":"Iakhine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irit","family":"Chorna-Ornan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy","family":"Zars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Elia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi","family":"Selinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baruch","family":"Minke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Hyde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2004,3,10]]},"reference":[{"key":"2023041303054156000_24.10.2516.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6072"},{"key":"2023041303054156000_24.10.2516.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00091-X"},{"key":"2023041303054156000_24.10.2516.3","unstructured":"Ashburner M (1989) Drosophila: a laboratory manual. 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